For some of you, the September 4^th NFL kickoff game between the Dallas Cowboys and Super Bowl champion Philadelphia Eagles can’t come fast enough. And, if that’s you, then it’s time to start handicapping the opening week of the 2025-26 NFL season.

You really can’t go wrong with planning your NFL bets in advance. Sure, we still have a lot of data points to factor in like the entire slate of NFL Preseason action. Yet, let’s not dismiss the opening NFL odds for Week 1 because there could be some hidden value there.

With that said, let’s take our first look at the NFL Week 1 schedule and make our early NFL picks for the opening week of the upcoming season.

NFL Week 1 Schedule

NFL Week 1 Odds

Oddsmakers wasted no time putting out sharp numbers. The biggest Week 1 favorites are the Denver Broncos over the Tennessee Titans, the New England Patriots against the Las Vegas Raiders, and the New Orleans Saints hosting the Arizona Cardinals.

Some of the closest spreads include Green Bay Packers vs. Detroit Lions, Miami Dolphins vs. Indianapolis Colts, and Baltimore Ravens vs. Buffalo Bills on Sunday night. For bettors, these near pick’em games often deliver value on the NFL moneyline.

If you like dogs, keep an eye on the NFL underdogs page. And don’t forget to compare numbers across the best sports betting sites before making a move.

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NFL Week 1 Predictions

Let’s take a look at the full Week 1 slate of matchups and make our early NFL picks for each game.

Dallas Cowboys vs. Philadelphia Eagles Odds

The Philadelphia Eagles come into Thursday Night Football for Week 1 riding high after a Super Bowl win and a dominant sweep of the Cowboys last season. In those two matchups, Philadelphia outscored Dallas 75-13, with Saquon Barkley powering the ground game. Barkley led the NFL in rushing attempts, yards, and yards per game last year, finishing with over 2,500 yards by season’s end and topping 118 yards in each playoff game. Against a Dallas defense that ranked fourth-worst against the run, Barkley is set up for another big opener.

Quarterback Jalen Hurts adds another dynamic layer to the Eagles’ attack. He rushed for 630 yards in the 2024 regular season and another 194 in the playoffs, showing that he remains one of the toughest dual-threat players to defend. Hurts gashed Dallas in limited action last year and gives Philadelphia a proven option to extend drives even if Barkley is bottled up early. Add in the Eagles’ 11-game home winning streak, and it’s no surprise oddsmakers made them touchdown favorites at Lincoln Financial Field.

Dallas, meanwhile, is eager to bounce back after a lost year with Dak Prescott sidelined for most of the season. Prescott’s return gives the Cowboys stability, and the front office surrounded him with new weapons. Wideout George Pickens joins CeeDee Lamb to form a dangerous duo, and Dallas should test an Eagles secondary that lost veteran Darius Slay and may rely on inexperienced players like Sydney Brown. If Prescott can get time, Dallas has the firepower to hang around.

Still, the key difference is in the trenches. Philadelphia dominated the line of scrimmage in both meetings last year and has the deeper roster on both sides of the ball. Dallas may keep it closer with Prescott back, but the Eagles’ ability to control tempo with Barkley and Hurts gives them the advantage.

This opening week matchup marks the 132^nd time that these rivals have played against each other. The Cowboys lead the series with a 74-58 record. However, the Eagles swept Dallas last season and outscored them 75 to 13.

Dallas Cowboys vs. Philadelphia Eagles Predictions

Philadelphia is riding an 11-game home win streak and has the better overall roster. The defending champs are built to avoid a letdown, and Barkley’s matchup against a weak Dallas run defense is a reliable edge. Backing the Eagles outright is the safest play.

Both meetings last season were blowouts, and Philadelphia covered easily. With Prescott back, Dallas should score more, but the Eagles’ offensive line and rushing attack are still mismatches. Expect Philadelphia to win by a touchdown or more, making -7 a solid play.

Dallas’ improved passing game with Prescott and Pickens should push the pace, while the Eagles are capable of putting up points in bunches. Philadelphia averaged over 37 points in the two meetings last year, and even a modest Dallas improvement should help the Over clear. With offensive playmakers on both sides, the game script leans toward a shootout.

Philly is 5-1 SU and 5-1 ATS in home games versus Dallas. They went 11-0 SU at home last season.

Bet: Philadelphia Eagles (-325), Eagles -7 (-110), Over 46.5 (-110)

Kansas City Chiefs vs. Los Angeles Chargers Odds

The first NFL International Game of the season is a battle of AFC West rivals. Although the Los Angeles Chargers are the home team, both squads will be playing on the road in Sao Paulo, Brazil.

The Chiefs and Chargers have played against each other 130 times, with just one postseason matchup. The Kansas City Chiefs hold the advantage with a 71-51-1 all-time record. However, they have dominated the Chargers in recent years.

The big question for Kansas City is whether Travis Kelce can bounce back after his least productive season as a starter. He’ll be leaned on heavily alongside young targets like Xavier Worthy. Mahomes has found ways to win despite pressure before, but the Chiefs need better balance to avoid another year of inconsistent play.

On the other side, Los Angeles has a new look with running backs Najee Harris and Omarion Hampton added to the backfield. Harris should bring physicality to a Chargers offense that already features Justin Herbert, who is coming off one of his best seasons. Second-year wideout Ladd McConkey also gives Herbert a new weapon to pair with the returning Keenan Allen. The Chargers ranked first in scoring defense a year ago, but the departures up front will test their depth.

The international stage adds an unpredictable element, but Kansas City has dominated this rivalry lately, winning seven in a row. Even so, most of those games have been tight, and the Chargers have the offensive talent to make this another down-to-the-wire divisional clash.

Kansas City has won seven straight games over Los Angeles. Last year, the games were decided by one score as the Chargers appear to have closed the gap.

Kansas City Chiefs vs. Los Angeles Chargers Predictions

Kansas City has proven it knows how to win close games against the Chargers, taking seven straight in the series. Mahomes has the experience edge in a neutral-site opener, and with Andy Reid scheming, the Chiefs are the safer play to win outright.

While Kansas City often wins, Los Angeles usually keeps it tight. Four of the last five meetings were decided by a field goal or less, and with Herbert’s weapons improved, the Chargers are a strong bet to cover the number even in defeat.

Both teams have the offensive firepower to push this game past the mid-40s. Mahomes will create big plays regardless of pressure, while Herbert has more than enough weapons to answer back. With explosive players on both sidelines, this has the feel of a shootout that clears the posted total.

Bet: KC Chiefs -148, Chargers +3 (-110), O 44.5 (-110)

Tampa Bay Buccaneers vs. Atlanta Falcons Odds

The Tampa Bay Buccaneers and Atlanta Falcons renew their NFC South rivalry in Week 1. The Bucs held off the Atlanta Falcons to win the title. So, what do the NFL schedule makers do? They pit the two rivals in a Week 1 matchup. Now the Bucs enter as slight road favorites, laying 2.5 points at Mercedes-Benz Stadium.

For Tampa Bay, the story has been offensive improvement. After ranking 20th in offensive DVOA in 2023, the Bucs jumped into the top 10 last season, with Baker Mayfield taking a step forward under coordinator Liam Coen. Even with Coen gone, Tampa Bay’s offensive core is intact, and Mike Evans is always a reliable weapon downfield. The defense, though not as dominant as in years past, remains opportunistic and disciplined.

The Falcons, meanwhile, have reasons for optimism under new offensive coordinator Zac Robinson. Atlanta climbed from 24th to 14th in offensive DVOA last year and has one of the most promising young offensive cores in the league with Michael Penix Jr., Bijan Robinson, Drake London, and Kyle Pitts all returning. The Falcons’ defense also showed growth late in the season, though consistency is still a question.

With both offenses capable of putting points on the board, this divisional showdown could be one of the more entertaining games of the Week 1 slate. Tampa Bay holds the experience advantage, but Atlanta’s track record against the Bucs in 2024 makes this anything but one-sided.

Tampa Bay Buccaneers vs. Atlanta Falcons Predictions

Divisional home underdogs have historically been profitable early in the season, and Atlanta fits the mold here. They beat Tampa Bay twice last year and have enough offensive balance to keep it close again.

While the Falcons may cover, Tampa Bay has the steadier roster and more proven quarterback play. If the game comes down to late drives, Mayfield and Evans are the safer bet to secure a narrow win.

Both teams improved offensively in 2024, and their defenses aren’t strong enough to expect a low-scoring grind. With skill players on both sides and recent history of higher-scoring games, the Over is the right angle.

Bet: Tampa Bay -142, Falcons +2.5 (-110), O 47.5 (-110)

Cincinnati Bengals vs. Cleveland Browns Odds

Joe Burrow enters this Week 1 AFC North clash looking like he’s on the cusp of being the league’s best quarterback. Fresh off a career year with nearly 5,000 passing yards and 43 touchdowns, Burrow has a full arsenal of weapons in Ja’Marr Chase, Tee Higgins, and a deep receiving corps. The concern remains the offensive line, which still struggles in pass protection. That could be a problem against a Cleveland front built around Myles Garrett.

The Browns doubled down on pass rush help in 2025, adding first-round pick Abdul Carter and free-agent Maliek Collins to bolster Garrett and Julian Okwara. This unit is already one of the league’s best at generating pressure, and it will test Burrow early. Still, Burrow has shown time and again he can overcome sacks and extend plays, keeping Cincinnati’s offense moving even under fire.

Cleveland’s offense is less stable, with Deshaun Watson sidelined. The Browns have a carousel of veterans and rookies to lean on, but none offer the upside that Burrow brings on the other sideline. The running game should provide some resistance, but Cincinnati’s defense has the speed to keep Cleveland from grinding out long drives.

History also favors the Bengals. Cincinnati has controlled this matchup recently, and with Burrow in form, they enter as deserving road favorites. The Browns’ defense may slow things down early, but Cincinnati’s firepower should eventually win out. The Bengals have been plagued by slow starts in recent years. As a result, I expect them to come out and make a statement with a dominant showing to open 2025.

Cincinnati Bengals vs. Cleveland Browns Predictions

With Cleveland shorthanded at quarterback, the safer play is backing Burrow and the Bengals outright. Cincinnati has the more reliable offense, and Burrow’s ability to create explosive plays should separate them in the second half.

Even with Cleveland’s strong pass rush, the Bengals’ talent at wide receiver is a mismatch against the Browns’ secondary. Burrow has covered this type of number before, and Cincinnati’s defense should give the offense enough opportunities to extend the lead.

Both teams are built to score despite their flaws. Burrow’s offense should hit on big plays, while the Browns’ rushing attack and possible short-field turnovers can contribute to points. Even if Cincinnati controls the game, Cleveland’s ability to punch back makes the Over the right side.

Bet: Bengals -6 (-110), Bengals -270 ML, Over 47.5 points (-115)

Miami Dolphins vs. Indianapolis Colts Odds

The Miami Dolphins are looking to snap a skid against the Indianapolis Colts that stretches back to 2019. They’ve dropped multiple straight in the series, including a 16–10 loss last year when Tua Tagovailoa was sidelined. This time, Tagovailoa is healthy and paired with his dynamic receiving duo of Tyreek Hill and Jaylen Waddle, giving Miami one of the most explosive passing attacks in the league.

The Dolphins also invested in the trenches this offseason, drafting lineman Jonah Savainaea to add muscle up front. That improvement should help buy Tagovailoa more time against a Colts defense that, while solid, has shown vulnerability against high-octane passing games. The concern for Miami is on the other side of the ball, where injuries have thinned the secondary. That could leave them vulnerable if Indianapolis forces the Dolphins into shootout mode.

The Colts enter with a reliable offensive foundation thanks to Jonathan Taylor, one of the league’s premier running backs. Taylor can carry the load if the passing game struggles, giving Indy a stable floor. At quarterback, Daniel Jones is expected to start, though Anthony Richardson could see action depending on how the season unfolds. Either way, the Colts’ offensive upside is limited compared to Miami’s firepower.

Given Miami’s speed advantage at the skill positions and Tagovailoa’s efficiency when healthy, the Dolphins are well-positioned to flip the script in this series. If they can protect Tua, Miami has every chance to put up 30+ points in Lucas Oil Stadium.

Miami Dolphins vs. Indianapolis Colts Predictions

Miami hasn’t beaten the Colts in years, but that changes with Tagovailoa back. With Hill and Waddle stretching the field, the Dolphins are simply too explosive for Indianapolis to keep pace over four quarters.

With such a tight line, taking the Dolphins against the number is essentially a safer version of the ML bet. Miami’s offense has the upside to win outright, and the points provide extra insurance if it’s close late.

Both teams bring strong rushing and passing elements, and Miami’s thin secondary raises the odds of Indy finding chunk plays. Combine that with the Dolphins’ ability to hit big strikes, and this game has shootout potential. Expect points to pile up.

Bet: Dolphins +1.5 (-102), Dolphins +102 ML, Over 46.5 points (-118)

Las Vegas Raiders vs. New England Patriots Odds

The Mike Vrabel era starts in New England with a tricky Week 1 matchup against the Las Vegas Raiders. The Patriots finished last in the AFC East a year ago, but with a favorable schedule and a new identity under Vrabel, they’re looking to flip the script. Rookie quarterback Drake Maye will get his first NFL start, and the pressure of opening at home could cut both ways.

Las Vegas has its own changes with Pete Carroll now at the helm and Geno Smith taking over at quarterback. The Raiders finished last in the AFC West in 2024 but have a defensive front that should cause trouble against New England’s line. Injuries hammered the Raiders last year, and if they’re healthier, this defense could resemble the group that ranked top ten in pressure win rate two seasons ago.

The Patriots will try to lean on their defense and running game to support Maye. New England’s offense ranked 30th in DVOA last season, so early struggles are likely. If the line can’t hold up, Maye will face heavy heat from a pass rush built to exploit mistakes.

This has the feel of a grinder at Gillette Stadium. The Patriots may find a way to win behind their defense, but it’s tough to see either side running away with it.

Las Vegas Raiders vs. New England Patriots Predictions

Pete Carroll has a strong track record as a short underdog, and Geno Smith has enough experience to keep the Raiders inside the number. With Las Vegas’ defensive front creating pressure, this looks like a tight contest.

While the Raiders can cover, the Patriots have home field and the better defense. Vrabel’s group should make just enough plays to grind out a win in his debut.

Neither team has an offense you can trust, and both defenses should control most of the afternoon. With Maye in his first start and Las Vegas still limited offensively, the Under is the sharp side.

Bet: Raiders +3 (+118), Patriots -148 ML, Under 42.5 points (-105)

Arizona Cardinals vs. New Orleans Saints Odds

The Arizona Cardinals enter Week 1 looking to bounce back after narrowly missing the playoffs last season. Despite a 6–4 start, they stumbled down the stretch, but Kyler Murray remains one of the league’s most dynamic quarterbacks. His ability to extend plays and attack downfield will be tested against a New Orleans defense that ranked just 23rd in DVOA last year.

For the New Orleans Saints, the Kellen Moore era begins with second-year quarterback Spencer Rattler under center. It’s a tough assignment, especially against an Arizona defense that finished 14th in DVOA despite facing one of the league’s hardest schedules in 2024. Rattler has talent, but growing pains are expected behind a shaky offensive line and a roster that won only three games after Week 2 last season.

Arizona’s defense matches up well with the Saints, but the Cardinals’ offense should be the difference. Murray has struggled against big road numbers historically, but his dual-threat ability and an improved supporting cast should give Arizona the edge. New Orleans will likely lean on the run game early to support Rattler, but if they fall behind, the pressure on the rookie could lead to mistakes.

Overall, this matchup tilts heavily toward Arizona’s experience and stability at quarterback. The Cardinals are the stronger team in all three phases and should have enough firepower to handle a rebuilding Saints squad in the Superdome.

Arizona Cardinals vs. New Orleans Saints Predictions

With Murray under center against one of the NFL’s worst teams, Arizona holds a massive advantage. The Cardinals’ defense is solid enough to keep the Saints in check while Murray provides the spark. Backing the Cardinals outright is the safest play.

The Saints are in transition with Rattler, and mistakes are bound to happen. Arizona has covered seven straight September road games, and with Murray’s playmaking ability, they’re positioned to win by at least a touchdown.

Despite Arizona’s defense being steady, Murray’s explosiveness and the potential for Saints turnovers create scoring opportunities. If the Cardinals build an early lead, Rattler will be forced to throw, increasing the chance of big plays on both sides. That sets this game up to push past the total.

Bet: Cardinals -6.5 (-110), Cardinals -278 ML, Over 42.5 points (-108)

Pittsburgh Steelers vs. New York Jets Odds

Aaron Rodgers’ return to MetLife Stadium headlines this matchup, but this time he’ll be wearing a different uniform. After a disastrous 2024 season with the New York Jets that ended in frustration and inconsistency, Rodgers was dealt to the Pittsburgh Steelers. Now he gets a chance to open the season against his former team, a revenge spot with plenty of drama.

The Steelers enter 2025 with sky-high expectations thanks to Rodgers and a reinforced roster that includes D.K. Metcalf, Jalen Ramsey, and Jonnu Smith. Pittsburgh’s defense was already elite, finishing first in pressure rate last year and holding opponents to just 17.1 points per game. With T.J. Watt and Alex Highsmith healthy, this unit is built to dominate weaker offensive lines like New York’s.

The Jets are turning to Justin Fields, hoping his mobility can offset protection issues. New York ranked just 16th in pass-blocking grades last season and 21st in offensive DVOA, and they’ll be tested immediately by a ferocious Pittsburgh pass rush. Fields can create plays on the ground, but sustaining drives against this Steelers defense will be a tall order.

Rodgers, meanwhile, has every reason to deliver in this spot. After an ugly exit from New York, he now has the tools and support to succeed. With one of the league’s most complete defenses backing him up, the stage is set for the Steelers to start strong.

Pittsburgh Steelers vs. New York Jets Predictions

Rodgers is motivated to beat his old team, and Pittsburgh’s defense is too stout to let the Jets hang around. The revenge angle combined with Pittsburgh’s roster upgrades makes the ML a safe play.

The Jets’ offensive line is a nightmare matchup against Watt and Highsmith. With Rodgers protected better and supported by new weapons, Pittsburgh should win this game by at least a touchdown.

While both defenses are strong, the number here is very low. Rodgers should get enough done to push Pittsburgh into the 20s, and Fields’ scrambling ability plus garbage-time potential gives New York a chance to add points. In today’s NFL, 38 is a modest bar, and this game projects to sneak Over.

Bet: Steelers -3 (-102), Steelers -155 ML, Over 38 points (-108)

New York Giants vs. Washington Commanders Odds

This will be an intriguing NFC East battle between two long-time rivals. The Washington Commanders enter Week 1 with playoff expectations after a 12-win campaign in 2024. Washington finished the season strong, clearing its win total with ease and advancing deep into the postseason. The Commanders have dominated this series recently, winning both meetings last year behind an offense that consistently moved the ball.

The New York Giants, on the other hand, are in a rebuild after a 3–14 season. They made changes under center by signing Russell Wilson and Jameis Winston, hoping experience can stabilize an offense that ranked near the bottom of the league in most categories. New York’s rushing attack gave Washington trouble last season, topping 125 yards in both meetings, but their defense remains a liability after ranking 23rd in DVOA.

Washington should look to establish the run early and set up play-action to exploit New York’s secondary. The Commanders’ defensive front isn’t elite, but against a Giants team breaking in a new QB situation, it should generate enough pressure. With more continuity on both sides of the ball, Washington is the more reliable option to open the year.

This NFC East rivalry has historically been close, but Washington’s home-field advantage and roster stability tilt the balance. Expect the Commanders to dictate tempo and control the game flow from start to finish.

New York Giants vs. Washington Commanders Predictions

Washington is the superior roster across the board, and at home, they should avoid any surprises. The Commanders’ offense has too many weapons for New York to keep pace. ML is the safest way to back the favorite.

The Commanders won both meetings last season and enter this year with higher expectations. The Giants’ shaky defense combined with questions at quarterback makes it tough to see them keeping this inside a touchdown. Laying the points is the sharper side.

While Washington should score consistently, New York’s rushing game and potential late scores make the Over attractive. Both teams cleared 125 rushing yards in head-to-head games last season, and divisional openers often see more points than expected. With Washington’s defense vulnerable to breakdowns, the Over 45.5 is live.

Bet: Commanders -6 (-108), Commanders -265 ML, Over 45.5 points (-112)

Carolina Panthers vs. Jacksonville Jaguars Odds

The Carolina Panthers enter 2025 with optimism, but they’ll be tested right away in a road trip to Jacksonville. Bryce Young closed last year on a high note and has a stronger supporting cast of young wide receivers after Carolina dealt veteran Adam Thielen back to Minnesota. The move signals confidence in players like Tetairoa McMillan, Xavier Legette, and Jalen Coker, but the group is still largely unproven at the NFL level.

Carolina’s offensive line is solid and should give Young time to work, but their defense remains a work in progress. The Panthers are loaded with fresh faces and could develop into a respectable unit, but expecting immediate chemistry in Week 1 feels ambitious. That side of the ball may be especially vulnerable against Trevor Lawrence.

The Jaguars are banking on a bounce-back year from Lawrence, who returns healthy after an injury-shortened season. With Liam Coen now running the offense in his first head coaching role, Jacksonville is hoping for a more consistent attack. Lawrence has already received a contract extension, and the expectation is that he’ll look far more like the steady passer from two years ago than the quarterback who stumbled to a 2–8 mark as a starter in 2024.

Playing at home and with a more stable roster, Jacksonville looks poised to control the matchup. Carolina’s young playmakers are intriguing, but Jacksonville’s mix of proven talent and renewed health makes them the safer pick.

Carolina Panthers vs. Jacksonville Jaguars Predictions

Jacksonville has the more complete roster and the better quarterback situation. Lawrence’s return to full strength gives the Jaguars a clear edge against a Carolina team still figuring out its identity.

The Panthers’ inexperience at receiver and defensive inconsistency make them a tough team to trust on the road. Jacksonville should cover this small number at home.

Carolina’s defense may be untested, but Jacksonville isn’t built for track meets, and the Panthers’ passing game is still a work in progress. Expect a lower-scoring game where the Jaguars do just enough to separate.

Bet: Jaguars -3 (-110), Jaguars -162 ML, Under 46.5 points (-110)

Tennessee Titans vs. Denver Broncos Odds

The Denver Broncos are coming off a 10-win season and a playoff berth, and they’ll open 2025 at home against the Tennessee Titans. Denver’s defense ranked among the league’s best in 2024, and with Sean Payton still pulling the strings, the Broncos are again expected to be in the AFC playoff mix.

The Titans, meanwhile, are breaking in rookie quarterback Cam Ward after effectively moving on from Will Levis. Ward is talented, but it’s a steep ask for any rookie to walk into Mile High in Week 1 and handle one of the NFL’s nastiest defenses. Tennessee finished 3-14 last season and posted the league’s worst ATS mark, covering just 12% of the time. This team is rebuilding, and it shows.

Denver will lean on balance. Bo Nix provides steady quarterback play, the running game keeps defenses honest, and the defense forces opponents into mistakes. Against a Titans roster that finished 31st in offensive DVOA and dead last in special teams, the Broncos should control field position and tempo throughout.

This matchup looks like a classic early-season mismatch. Denver is established, Tennessee is still piecing things together, and a road trip to Denver in September rarely goes well for visiting teams.

Tennessee Titans vs. Denver Broncos Predictions

Denver closed as a favorite eight times last year and covered all eight. Against a rookie quarterback and one of the NFL’s weakest rosters, they’re in position to cover another big number at home.

While the spread is the bolder play, Denver on the ML is a safe parlay piece. With the defense holding such a big edge, an upset isn’t in the cards.

Both defenses have strengths, and Tennessee’s offense is unlikely to contribute much to the scoreboard. Denver should win comfortably, but a grind-it-out style points to the Under.

Bet: Broncos -7.5 (-115), Broncos -395 ML, Under 41.5 points (-108)

San Francisco 49ers vs. Seattle Seahawks Odds

The Seattle Seahawks will open at home against the San Francisco 49ers, looking for a statement win in Mike MacDonald’s second year. Seattle finished 10-7 last season but lost a tiebreaker to the Rams, missing the postseason. San Francisco stumbled to 6-11 amid a rash of injuries but now enters 2025 with one of the league’s easiest schedules and a healthy core.

Seattle’s defense showed flashes last season, improving in the back half of the year, but struggled badly against top-tier offenses. In three games against teams ranked top five in offensive DVOA, the Seahawks gave up 30+ points each time. That doesn’t bode well with Christian McCaffrey, Brandon Aiyuk, and George Kittle all expected to be on the field together in Week 1 after missing various matchups last season.

That said, Seattle has been one of the league’s toughest September home teams. They’ve won six straight September games at Lumen Field and will have the crowd fully behind them for this NFC West rivalry. Newcomer Sam Darnold has the weapons to exploit a 49ers defense that was middling against the pass last season. Jaxon Smith-Njigba gives Seattle the ability to stretch the field, while Kenneth Walker III adds balance on the ground.

This game has all the makings of a shootout. San Francisco has the better roster on paper, but Seattle’s home-field edge and ability to score quickly make this one of the trickiest games on the slate.

San Francisco 49ers vs. Seattle Seahawks Predictions

Seattle has been lethal at home early in the season and matches up well enough offensively to pull off the outright upset. Geno Smith should be able to move the ball against San Francisco’s secondary.

Even if Seattle doesn’t win, they’re live to keep it within a field goal. In divisional games, especially in Week 1, small spreads often come down to late drives — exactly the spot where home-field matters most.

Both teams have firepower and Seattle’s defense hasn’t proven it can slow down elite offenses. Expect points from both sides and a final score that sails over the number.

Bet: Seahawks +2.5 (-110), Seahawks +114 ML, Over 44.5 points (-108)

Detroit Lions vs. Green Bay Packers Odds

The Week 1 showdown between the Detroit Lions and Green Bay Packers features two NFC North heavyweights with postseason expectations. The Lions are coming off a 15-win campaign but saw their Super Bowl hopes dashed in the divisional round after key defensive injuries piled up. Dan Campbell’s group has made its mark as one of the NFC’s most physical teams and returns nearly its entire offensive core.

Green Bay sneaked into the playoffs as the NFC’s seventh seed for the second straight year, but consistency was a major issue. Jordan Love showed flashes, particularly in the second halves of games, where he has historically performed better against the spread. Still, against a fully loaded Detroit team, the Packers face an uphill battle even at Lambeau Field.

Detroit dominated Green Bay early in their two meetings last season, outscoring the Packers 34-10 in the first halves. The Lions’ ability to control games early stems from their balanced attack. Jared Goff is surrounded by a deep arsenal of weapons – Amon-Ra St. Brown, Jameson Williams, and rookie Isaac TeSlaa out wide – while the running back tandem of Jahmyr Gibbs and David Montgomery gives Detroit one of the best ground games in football.

On defense, the Lions still need to improve against the pass, but with Aidan Hutchinson leading a ferocious front seven, they’re more than capable of pressuring Love into mistakes. If Green Bay falls behind early, history suggests it will be difficult to mount a comeback against Campbell’s disciplined squad.

Detroit Lions vs. Green Bay Packers Predictions

Detroit has been a first-half machine under Campbell, posting a 50-28-2 ATS record in regular-season first halves since he arrived. Their ability to start fast should neutralize Lambeau’s home-field advantage and make Detroit the right side catching points.

The Lions won 15 games last year and still have one of the NFC’s deepest rosters. Taking them outright provides better value than a short spread, especially considering they’ve matched up well against Green Bay in recent seasons.

Both offenses can score in bunches. The Lions have the firepower to put up 30+, while the Packers’ offense is good enough to trade blows at home. With Green Bay’s defense still unproven and Detroit’s secondary vulnerable, the over looks like the sharpest total bet.

Bet: Lions +1.5 (-108), Lions +105 ML, Over 48.5 points (-115)

Houston Texans vs. Los Angeles Rams Odds

The Los Angeles Rams surged back into the playoff picture last season, winning nine of their last 12 games after a sluggish start. Sean McVay’s offense will look a little different in 2025 – Cooper Kupp has moved on, but the Rams filled that void in a big way by bringing in Davante Adams to pair with breakout star Puka Nacua. That duo gives Matthew Stafford one of the NFL’s most dangerous receiving tandems, ensuring the Rams’ passing attack won’t miss a beat.

Houston, meanwhile, won the AFC South for the second straight year but did so with more defensive grit than offensive explosion. After ranking 14th in offensive DVOA in 2023, the Texans plummeted to 26th last season. Injuries played a role, but even with C.J. Stroud under center, the offense struggled to generate consistency. Still, their defense remained a bright spot, finishing top-10 against the pass.

The matchup looks like a clash of styles: the Rams’ high-powered pass game against Houston’s bend-but-don’t-break defense. If the Texans’ young offensive line can hold up, Stroud has the weapons to keep this game competitive. But the Rams are deeper, better coached, and tougher to beat at SoFi when fully healthy.

Houston Texans vs. Los Angeles Rams Predictions

Houston’s defense gives them a fighting chance to stay inside this number. They’ve covered in several spots as road underdogs against NFC teams, and their ability to generate pressure should at least slow Stafford down enough to prevent a blowout.

While Houston may hang around, Los Angeles has too many proven playmakers. Backing the Rams to win outright – especially at home – is the safer play.

Both defenses are stronger than their opposing offenses. The Rams thrive against weak offensive units (6-1 ATS vs. bottom-tier offenses last year), while Houston lacks the consistency to guarantee points. A grindy, lower-scoring game favors the Under.

Bet: Texans +2.5 (-108), Rams ML -142, Under 44.5 points (-115)

Baltimore Ravens vs. Buffalo Bills Odds

This Sunday Night Football game is a rematch of last season’s divisional round thriller, when Buffalo edged Baltimore 27–25. Oddsmakers have the Bills as narrow 1.5-point favorites, but there’s plenty of reason to expect another high-scoring shootout.

Lamar Jackson continues to thrive as an underdog, carrying an incredible 12–2 ATS record in that role over his career. Baltimore never punted in the playoff loss to Buffalo, scoring or turning the ball over on every drive, and their offense still profiles as one of the most efficient units in football. The Ravens’ run game should challenge Buffalo’s front seven, while Zay Flowers and Mark Andrews stretch the secondary.

Buffalo, meanwhile, leans on Josh Allen’s dual-threat ability. Stefon Diggs is gone, but Keon Coleman adds size on the outside, and Dalton Kincaid looks primed for a breakout. The Bills’ defense retooled with some offseason signings, but they may not be able to slow a Baltimore team that ranked No. 1 in offensive DVOA against one of the NFL’s toughest schedules last year.

With both teams carrying explosive playmakers and QBs who can win games with their legs or arms, this projects as one of the highest-scoring games of Week 1.

Baltimore Ravens vs. Buffalo Bills Predictions

Jackson has a proven track record of keeping these games close, and his ATS record as a pup makes Baltimore the smart side on the spread.

In a tight contest, home-field advantage and Josh Allen’s late-game heroics give Buffalo the slight edge outright.

Neither defense has enough to fully contain these offenses. With their last playoff meeting hitting 52 points, the over is the best way to attack this total.

Bet: Ravens +0.5 (-105), Bills -120 ML, Over 51.5 points (-112)

Minnesota Vikings vs. Chicago Bears Odds

The Ben Johnson era kicks off in Chicago, but the Week 1 Monday Night Football spotlight may shine brighter on the visiting Vikings. Minnesota is coming off a 14-win campaign in 2024, easily clearing its preseason expectations and positioning itself as one of the NFC’s top contenders. Chicago, on the other hand, struggled to just five wins in Caleb Williams’ rookie season, often undone by poor offensive line play and a leaky defense.

The Bears did make upgrades in the trenches this offseason, signing Grady Jarrett and Dayo Odeyingbo to bolster the defensive front. Still, J.J. McCarthy enters his first NFL road start with plenty of weapons, and Minnesota’s offense should be able to exploit Chicago’s secondary. Justin Jefferson remains a matchup nightmare, and the Vikings’ supporting cast is deep enough to stretch the field against a defense that allowed 30 points in their last Soldier Field matchup.

History doesn’t do Chicago many favors here, either. The Bears have lost nine of their last 10 games against NFC opponents and fell twice to the Vikings in 2024. While Caleb Williams is expected to show improvement, he’ll need near-perfect execution to outduel Minnesota’s firepower.

Minnesota Vikings vs. Chicago Bears Predictions

Minnesota’s offense has too many ways to attack, and Chicago hasn’t shown it can keep up against high-end NFC competition.

Laying the short price on the outright win is a safe way to back the more proven team.

With both defenses vulnerable, the talent at QB and WR for both sides should push this total over. Minnesota’s scoring ceiling makes this play particularly appealing.

Bet: Vikings -1.5 (-112), Vikings -122 ML, Over 43.5 (-102)

NFL Week 1 Best Bets

The following is our best bets for NFL Week 1:

• Philadelphia Eagles -7 vs. Cowboys (-108)
• Buffalo Bills vs. Baltimore Ravens Over 51.5 (-112)
• Miami Dolphins Moneyline vs. Colts (+102)

The Eagles open up the season at home against a disoriented Dallas team who just traded their best player. I love the Eagles in this matchup to blow out the Cowboys.

Buffalo and Baltimore have been two of the highest scoring teams over the last few years. I expect that trend to continue as they open up the season hitting the Over in their SNF game.

I don’t believe in any team with Daniel Jones as the starting QB. I see the Dolphins being slightly better than many pundits give them credit for. Miami should win this one by a comfortable margin.

If you follow our NFL best bets for Week 1 and put all three wagers into a parlay, then at the combined odds of +636, you would turn a $100 bet into about $736 total payout ($636 profit). For more parlay bets, check out our best NFL parlays for each and every week.