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Week 6 of the 2025 NFL season may be four months away, but it’s never too early to dig into the schedule, break down some lines, and make wildly premature predictions. These odds will shift between now and October: Training camp injuries, quarterback controversies, and whatever Aaron Rodgers says next will all impact the markets.

Before we dive in, catch up on our NFL Preseason coverage and start looking ahead to Super Bowl 60. For everything betting-related this season, check out our complete NFL betting guide, and don’t forget to visit our NFL picks page for every game this week.

2025 NFL Week 6 Schedule

NFL Week 6 Odds

The Philadelphia Eagles (-7) are the biggest road favorite of the week, opening as a touchdown favorite over the New York Giants on Thursday Night Football in a primetime NFC East matchup. If recent history is any guide, this could be a trap spot. Division ‘dogs have performed well against the spread over the years, particularly at home in primetime.

Another notable number: the Pittsburgh Steelers are laying 6.5 at home vs. Cleveland, showing little respect for the forever-rebuilding Browns. Meanwhile, the tightest line is Dallas -1.5 at Carolina, a legit toss-up.

Total-watchers should eye 49ers vs. Buccaneers (48.5) and Bengals vs. Packers (48.5) as two of the highest projected scoring games. If you’re chasing the lowest, look no further than Broncos vs. Jets (42.5), which could be a puntfest across the pond.

For more numbers, trends, and line movement, visit our full NFL odds hub, and don’t forget to scope out NFL underdog picks. You can also compare lines across top sports betting sites and tail our top handicappers all season long.

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NFL Week 6 Predictions

Let’s take a deeper dive into the odds and make our favorite NFL picks for each game on the Week 6 schedule

Philadelphia Eagles vs. New York Giants Odds

The reigning Super Bowl champion Philadelphia Eagles head into 2025 looking to defend their crown with most of the core intact. Despite some offseason losses on the defensive line – including the departures of Brandon Graham and Josh Sweat – the Eagles return Jalen Hurts, A.J. Brown, and one of the NFL’s most balanced rosters. They’ll open the year in prime time and play multiple spotlight games throughout the season, including this Week 6 Thursday Night Football matchup against the division rival New York Giants.

The front half of Philly’s schedule is packed with tests: trips to Kansas City, Tampa Bay, and Dallas, plus games against the Lions and Packers. With new defensive coordinator Vic Fangio stepping in, all eyes will be on whether the Eagles can maintain their dominance while reshaping the defense. But with Hurts healthy and weapons everywhere, it’s hard to see them taking much of a step back. This Week 6 trip to MetLife Stadium could be a tone-setter for the NFC East race.

The Giants are facing one of the league’s toughest schedules and enter the season hoping to finally stabilize the quarterback position. They’ll open with two straight road games and play five of their first six away from home, including matchups against the Commanders, Cowboys, and Chiefs. By the time they return to MetLife Stadium for this Week 6 showdown with the Eagles, we should have a much better idea of whether rookie Jaxson Dart is up to the task.

Philadelphia Eagles vs. New York Giants Predictions

After a 3–14 campaign in 2024, the Giants are banking on an infusion of youth and a more favorable injury outlook. The defense, anchored by Kayvon Thibodeaux, Dexter Lawrence, and rookie Abdul Carter, will have to punch above its weight class early on if New York hopes to stay competitive. Against the defending champs, containing Jalen Hurts and forcing mistakes will be key, but easier said than done. This is a brutal NFC East measuring stick early in the year.

While the Eagles are clearly the superior team, this is still a divisional road game on short rest. The total sits at 43.5, and given the familiarity and defensive strength on both sides, the under looks appealing.

Bet: Philadelphia Eagles (-278), Giants +7 (-110), Under 43.5 (-110)

Denver Broncos vs. New York Jets Odds

The Denver Broncos are embracing the spotlight in 2025, with five prime-time games and a trip to London in Week 6 against the Jets. After ending their playoff drought last season, Sean Payton’s squad is eager to prove it wasn’t a fluke. The team poured resources into revamping the defense, signing key free agents, and drafting standout CB Jackie Barron to deal with a brutal QB slate that includes Patrick Mahomes (twice), Justin Herbert, and Josh Allen. This London game is part of a tough first half that could define their season.

For the New York Jets, it’s about finding stability in the post-Aaron Rodgers era. New head coach Aaron Glenn starts the season with five of six games on the road, including this international trip.

The team is betting on Justin Fields to bounce back behind a retooled offensive line and new weapons. The Jets will need their defense to do the heavy lifting early, especially in matchups like this one against a playoff-tested Broncos team. With one of the league’s easiest overall schedules, how they survive September and October will dictate whether they’re still in the mix down the stretch.

Denver Broncos vs. New York Jets Predictions

The Denver Broncos are the better team in this game. They also have the better defense, which is going to be the difference maker for this matchup. Look for the Broncos to harass Fields all game long, and Bod Nix to make timely plays as the Broncos win this game. However, I like the Jets to cover the spread.

Denver Broncos (-278), Jets +6.5 (-110), Under 42.5 (-110)

Dallas Cowboys vs. Carolina Panthers Odds

The Dallas Cowboys are once again under the national spotlight in 2025, opening their season against the defending Super Bowl champion Eagles and playing a whopping four Thursday games overall. For new head coach Brian Schottenheimer, early success will be critical, especially with Dak Prescott returning from injury and looking to re-establish chemistry with CeeDee Lamb and his newest weapon, George Pickens. The Cowboys haven’t lost to the Panthers since 2007, winning six straight in the series.

This Week 6 road trip to Carolina falls in a potentially dangerous spot between games against the Jets and Commanders. While Dallas has had success away from home in recent years, they’ll need to stay sharp defensively to avoid letting Bryce Young find rhythm. Defensively, Micah Parsons leads a unit capable of dictating game flow, particularly against a young offense still in rebuild mode.

The Carolina Panthers, meanwhile, are hoping to take a step forward under head coach Dave Canales and third-year QB Bryce Young. After a 2-15 campaign in 2024, they’ve revamped their receiving corps and added top-10 pick Tetairoa McMillan to provide Young with another weapon. With one of the league’s softest schedules, this matchup against Dallas will serve as a key measuring stick for where the franchise is headed.

While the Cowboys should win, the Panthers are 5-1 ATS in their last six home games as underdogs. With a low spread and the Panthers’ defense playing better at home, this feels like a potential trap spot.

Bet: Dallas Cowboys (-122), Panthers +1.5 (-112)

Arizona Cardinals vs. Indianapolis Colts Odds

The Arizona Cardinals hope their 2025 schedule offers a springboard into playoff contention after a few flashes of relevance in 2024. They’ll face four first-round QBs and seven Heisman winners this year, so early-season momentum is key. This Week 6 trip to Indianapolis follows their bye, giving Kyler Murray and Arizona’s retooled defense a chance to reset before heading back into the grind. The Cardinals’ offense, now fully healthy and featuring a deep draft class, could make noise if the line holds up.

The Indianapolis Colts are looking to take a leap behind Anthony Richardson, who flashed occasional promise in Year 2 before injuries and inconsistency derailed his season. With back-to-back home games to start the year and another here in Week 6, Indy has a chance to rack up early wins and stay in the AFC South mix. The Colts quietly made upgrades on both lines and hope continuity on offense will help Richardson stay on the field and build chemistry with his young receiving corps.

Arizona Cardinals vs. Indianapolis Colts Predictions

Both teams could be frisky wildcard contenders in their respective conferences, and this Week 6 tilt might be more meaningful than expected by the time it rolls around. With Arizona coming off a bye and Indy finally enjoying some schedule stability, expect both sides to be aggressive and creative.

Arizona tends to play better with extra rest, and Indy has struggled against mobile QBs. This line is tight for a reason, but the edge might lie with Kyler and the Cards coming off a bye.

Bet: Arizona Cardinals (-120), Cardinals -1.5 (-110)

San Francisco 49ers vs. Tampa Bay Buccaneers Odds

The San Francisco 49ers enter 2025 with the NFL’s easiest projected schedule, but don’t expect a free ride. After falling short in the 2023 Super Bowl and failing to make the playoffs at all in 2024, Kyle Shanahan’s squad is facing pressure to finish the job. The defense looks elite, and with Brock Purdy firmly entrenched as QB1, the offense should hit the ground running. A midseason stretch with five straight games away from home will test their durability, and this Week 6 road game at Tampa Bay kicks off that gauntlet.

The Tampa Bay Buccaneers are aiming for a third straight division title and will try to break a losing streak against the Niners that dates back to 2018. Baker Mayfield returns alongside Mike Evans, who is chasing NFL history with a chance to become the all-time leader in consecutive 1,000-yard seasons. If the Bucs are going to stay in contention, this is a pivotal homestand, and one of their few games against legit NFC contenders.

San Francisco 49ers vs. Tampa Bay Buccaneers Predictions

Both teams are battle-tested and play with physicality, which could make for one of the grittiest showdowns on the Week 6 slate. San Francisco has had trouble staying healthy midseason, while Tampa has historically defended home turf well against West Coast opponents.

The Bucs play tight at home and the total here looks just a bit high. With two strong defenses and playoff implications looming, we lean toward a slugfest.

Bet: Tampa Bay Buccaneers (-125), Bucs -1.5 (-110), Under 48.5 (-110)

Cleveland Browns vs. Pittsburgh Steelers Odds

The Cleveland Browns are trying to bounce back from a disappointing 3–14 campaign that cost them the benefit of prime-time exposure. They’ll play the league’s hardest schedule in 2025 and open the season with brutal matchups against the Bengals, Ravens, and Packers. With uncertainty still looming at quarterback – whether it’s Joe Flacco, rookie Shedeur Sanders or someone else – Kevin Stefanski’s squad will need to win games in the trenches to stay afloat.

This Week 6 trip to Pittsburgh closes out a critical stretch for the Browns before their bye. Despite some promising talent on defense, Cleveland’s offense is a work in progress, and their recent history against the Steelers is rough. Myles Garrett and the front four will need to rattle Rodgers early to give the Browns any chance of stealing one on the road.

The Pittsburgh Steelers, on the other hand, are embracing a new era with Aaron Rodgers under center. After a disastrous 2024 with the Jets, Rodgers gets a fresh start in Pittsburgh, bringing both a massive spotlight and Super Bowl aspirations. The Steelers open the year with four road games in five weeks but return home here in Week 6 with a chance to assert dominance in the AFC North.

Cleveland Browns vs. Pittsburgh Steelers Predictions

Even with Rodgers acclimating to a new system, Pittsburgh’s defense remains elite, and Mike Tomlin continues to work miracles in tight matchups. With Cleveland still sorting through its identity, the Steelers should control this one from kickoff to clock-out.

The Browns have too many unknowns, and Pittsburgh will be fired up for Rodgers’ homecoming. Laying the points at -6.5 still offers value against a team in flux.

Bet: Pittsburgh Steelers (-278), Steelers -6.5 (-105)

Los Angeles Chargers vs. Miami Dolphins Odds

The Los Angeles Chargers face one of the most grueling travel schedules in the league this season, covering more than 37,000 miles. They’ll need to bring their best on the road, especially for this pivotal Week 6 matchup against a Dolphins team with playoff ambitions of their own. Jim Harbaugh is back for Year 2 and will count on Justin Herbert to carry an offense that should be more physical and better prepared for high-leverage spots like this one.

The Miami Dolphins are trying to bounce back from a 2024 collapse that saw them miss the playoffs despite high expectations. Mike McDaniel’s crew has one of the easiest schedules in the NFL, but it’s the early games like this that could define their path. With Tua Tagovailoa back healthy and an upgraded offensive line led by rookie Kenneth Grant, Miami will look to start strong before a rough midseason stretch.

Los Angeles Chargers vs. Miami Dolphins Predictions

The Herbert vs. Tua rivalry always draws attention, dating back to their 2020 draft class ties. While both QBs have had flashes of brilliance, neither has fully cemented their elite status. This matchup, which could factor into AFC Wild Card seeding, is a pressure cooker for two organizations hoping to prove they belong in the postseason.

Despite Miami’s upside, the Chargers’ pass rush and travel-hardened identity make them a good road bet. The Dolphins are 2-5 ATS in their last 7 games as home underdogs.

Bet: LA Chargers (-142), Chargers -2.5 (-112)

Los Angeles Rams vs. Baltimore Ravens Odds

The Los Angeles Rams enter 2025 aiming to prove last year’s playoff appearance was no fluke. Sean McVay’s team will have to navigate a long season that includes international travel and several East Coast swings. This Week 6 matchup against Baltimore comes just before their bye, making it a natural pivot point for the Rams’ season. With Matthew Stafford still under center and Cooper Kupp and Puka Nacua back healthy, this team has the firepower to keep up.

That said, the Baltimore Ravens present a brutal challenge. The Ravens are widely considered one of the top Super Bowl contenders entering 2025, with Lamar Jackson coming off another MVP-caliber campaign and the defense returning most of its core. They’ve got five prime-time games and open the season against four playoff teams from 2024. This game against the Rams is one of their few breathers, and they can’t afford to let it slip.

Los Angeles Rams vs. Baltimore Ravens Predictions

The key matchup will be whether the Rams’ offensive line can hold up against the Ravens’ relentless pass rush. Baltimore has a long history of bullying West Coast visitors, and with three straight road games coming up after this one, the Ravens need to stack wins early to stay ahead in the loaded AFC North.

The Rams will put up a fight, but Baltimore at home is a tough out. The total is high, but don’t count on a shootout.

Bet: Baltimore Ravens (-238), Ravens -5.5 (-112)

Seattle Seahawks vs. Jacksonville Jaguars Odds

The Seattle Seahawks enter a new era with Sam Darnold at quarterback and Mike Macdonald returning for his second season as head coach. The early part of the season will be a litmus test for Seattle’s retooled offense and whether its defense, once the team’s hallmark, can return to form. This Week 6 trip to Jacksonville comes right before the bye and could be a true tone-setter. If the Seahawks want to stay relevant in the NFC playoff picture, this is the type of game they need to steal.

The Jacksonville Jaguars are navigating one of the NFL’s most demanding travel slates in 2025, but at least they get this game at home. They’ll look to take care of business against a middling Seattle team as they try to stay competitive in the AFC South. With Trevor Lawrence healthy again and the addition of rookie WR Travis Hunter, the Jags’ offense could be significantly more explosive.

Seattle Seahawks vs. Jacksonville Jaguars Predictions

Both teams are fighting to climb out of the middle tier in their respective conferences. While Jacksonville has the on-paper edge, Seattle’s defensive upgrades and the unpredictability of Darnold make this matchup anything but a sure thing.

The Jags are slightly overvalued here. This has the feel of a coin-flip game. We’ll grab the points and lean dog.

Bet: Seattle Seahawks (+100), Seahawks +1.5 (-112)

Tennessee Titans vs. Las Vegas Raiders Odds

The Tennessee Titans are leaning into the future with rookie QB Cam Ward, who will face one of the toughest defensive fronts in the NFL in his first few starts. Ward and new coach Brian Callahan open the season on the road and then get this Week 6 trip to Vegas after a stretch of early AFC showdowns. Tennessee’s defense, led by Harold Landry III, will need to carry the load while Ward adjusts to the speed of the league.

The Las Vegas Raiders are hoping the addition of Pete Carroll helps spark some midseason consistency. Geno Smith takes over at QB and brings playoff experience, while the offensive focus shifts to dynamic rookie running back Ashton Jeanty. Las Vegas plays three straight home games before this matchup, and this will be a big one if they want to stay competitive in the AFC West.

Tennessee Titans vs. Las Vegas Raiders Predictions

Both teams are in transition, but Vegas appears better built to win now. The Raiders’ defense should be able to pressure Ward and limit the Titans’ offensive options, especially in a hostile environment.

Tennessee might keep it close for a while, but the Raiders are too balanced.

Bet: Las Vegas Raiders (-162), Raiders -3 (-115)

New England Patriots vs. New Orleans Saints Odds

The New England Patriots open a new era under head coach Mike Vrabel and face a favorable schedule to start, with three of their first four games at home. While their overall ceiling is still in question, the Patriots’ early stretch includes multiple winnable matchups, including this Week 6 home clash against the Saints. New England will likely be leaning on second-year QB Drake Maye, whose development could determine whether the Pats can overachieve.

The New Orleans Saints are breaking in rookie head coach Kellen Moore and potentially starting the season with either Tyler Shough or Spencer Rattler at quarterback. They’ll travel to Foxborough in the middle of a stretch where they face the Bills, Rams, and Bucs. While their schedule is light on prime-time games, it’s loaded with tough road trips that will test their young signal callers.

New England Patriots vs. New Orleans Saints Predictions

This matchup pits two franchises in transition and could carry wild-card implications down the line. It’s also one of the few spots where New England’s defensive line may be able to dominate the trenches.

At home against a rookie QB and a first-year head coach, the Patriots’ defense should do enough

Bet: New England Patriots (-162), Patriots -3 (-110)

Cincinnati Bengals vs. Green Bay Packers Odds

The Cincinnati Bengals are back in contention mode with a healthy Joe Burrow and one of the NFL’s most dangerous receiving trios. This Week 6 trip to Lambeau Field kicks off a pivotal three-game stretch that includes matchups against the Steelers and Ravens. If the Bengals want to stay in the AFC North title hunt, this is the kind of swing game they’ll need to win, especially with the Ravens looming just ahead.

The Green Bay Packers are hoping to build on their strong finish to the 2024 season. With Jordan Love entrenched as the starter and Matt LaFleur overseeing an offense that took a big step last year, Green Bay enters 2025 as one of the NFC’s most intriguing playoff threats. This is a rare opportunity for the Packers to start strong: They open with four of their first five games at home.

Cincinnati Bengals vs. Green Bay Packers Predictions

Both teams are capable of scoring in bunches, and this game could turn into a sneaky shootout if conditions are favorable. The Bengals haven’t played at Lambeau since 2017, but Burrow and company won’t shy away from the cold.

While Burrow is always live as an underdog, the Packers are 13-5 ATS in their last 18 home games. We’ll side with the steadier defense.

Bet: Green Bay Packers (-142), Packers -2.5 (-115)

Detroit Lions vs. Kansas City Chiefs Odds

The Detroit Lions are no longer sneaking up on anyone. After reaching the NFC title game and winning 15 games last season, Dan Campbell’s squad is entering 2025 with real expectations and real challenges. This Week 6 road trip to Kansas City is one of their toughest draws. With five prime-time games and one of the league’s hardest road schedules, Detroit needs every win it can get to stay on top of a loaded NFC North.

The Kansas City Chiefs are hunting for redemption after their Super Bowl LIX loss to the Eagles. Andy Reid and Patrick Mahomes are entering their usual contender mode, and the Chiefs will be tested by a midseason gauntlet that includes the Ravens, Cowboys, Texans, and these very Lions. They’ve been nearly unbeatable at Arrowhead in October, going 14-2 in Mahomes’ starts during the month.

Detroit Lions vs. Kansas City Chiefs Predictions

This game pits two of the league’s most complete rosters and creative play-callers against one another. The difference could come down to who executes better in the red zone, and whether the Lions’ defense can generate any pressure on Mahomes without blitzing.

This line is sharp, but with Detroit’s recent success and Kansas City’s history of slow starts, we lean toward the points.

Bet: Detroit Lions (+130), Lions +3 (-115)

Buffalo Bills vs. Atlanta Falcons Odds

The Buffalo Bills may have drawn one of the most favorable schedules of any contender, but that doesn’t mean they can coast. Their front-loaded slate includes five prime-time games in the first six weeks, and this Week 6 Sunday Night Football road game at Atlanta comes on a short week after a high-profile clash with Kansas City. Josh Allen and James Cook will look to keep Buffalo humming against a Falcons team trying to find its footing under new leadership.

The Atlanta Falcons have new life with second-year quarterback Michael Penix Jr. and a promising young core. This will be the Falcons’ second game back from their bye, and they’ll hope to catch a potentially tired Bills team looking ahead to tougher AFC showdowns. If Penix can push the ball downfield and the defense holds up early, Atlanta could hang around.

Buffalo Bills vs. Atlanta Falcons Predictions

Buffalo has historically struggled in domes and is 1–3 in its last four road games against NFC South opponents. Still, the talent gap here is significant, and the Bills know they can’t drop winnable games if they want to reclaim the AFC East.

Expect Allen and the Bills to roll, but the total may be ambitious if the Falcons stall early.

Bet: Buffalo Bills (-230), Bills -5.5 (-110), Under 48.5 (-110)

Chicago Bears vs. Washington Commanders Odds

The Chicago Bears enter the Week 6 Monday Night Football matchup, hoping that rookie head coach Ben Johnson can stabilize a franchise that’s lacked consistency in recent years. With five prime-time or standalone games on their schedule—including this one—Chicago is firmly in the national spotlight. No. 1 overall pick Caleb Williams will be facing off against a ferocious Washington defensive line here, and how he handles the pressure could set the tone for the Bears’ second half.

Chicago opens the season with a brutal stretch that includes the Vikings, Lions, Ravens, and Cowboys in the first five weeks. That makes this road trip to Washington a potential swing point. If Williams and Johnson’s offense can find rhythm, the Bears have enough firepower to hang. But they’ll need to protect the rookie QB better than they did during his early trials against NFC North foes.

The Washington Commanders are leaning into the Jayden Daniels era with high expectations. They’re projected to play the NFL’s most national games this year and boast a young, fast offense with breakout potential. Washington’s late-season schedule is loaded, so stacking early wins is crucial. This home game against Chicago is one they’ll be expected to control if they’re going to reach the postseason.

Chicago Bears vs. Washington Commanders Predictions

Both teams feature second-year quarterbacks and electric skill players, but Washington’s defense—and the home crowd—could tilt the scales. Rather than trust either side to cover, the total may be the safer play.

Bet: Washington Commanders (-198), Over 48.5 (-110)

NFL Week 6 Best Bets

• Steelers -6.5 (-105) vs. Browns
• Panthers +1.5 (-112) vs. Cowboys
• Under 48.5 (-110) in Eagles vs. Giants

These bets combine sharp trends with strong matchup edges. Parlay all three at standard odds and a $100 bet could return around $600.See more top picks in our NFL parlays of the week.