Tennessee Titans vs Indianapolis Colts Picks and Predictions September 21st 2025

Tennessee Titans vs Indianapolis Colts September 21st 2025

The Indianapolis Colts visit the Tennessee Titans in Week 3 of the 2025 NFL season. The game takes place at Nissan Stadium in Nashville, Tennessee, with kickoff set for 1:00 PM on CBS. The matchup is part of a full slate covered in our NFL Week 3 blog, where you can track team form and betting insights.

The Colts enter at 2-0 after winning both of their home games. On the other side, the Titans are searching for their first victory of the year, sitting at 0-2. Weather could play a role, with light rain expected on the outdoor field in Nashville.

Colts vs Titans Key Information

• Sport: Football
• Teams: Indianapolis Colts vs. Tennessee Titans
• Venue: Nissan Stadium in Nashville, TN USA
• Date: Sunday, September 21, 2025
• Betting Odds: Colts Moneyline -201, Titans Moneyline +169, Colts Spread -4.0 (-110), Titans Spread +4.0 (-108), Total Over 43.5 (-109), Total Under 43.5 (-111)

The Colts Can Win If…

The Indianapolis Colts are coming off a narrow 29-28 win over the Denver Broncos. Daniel Jones led the charge with 316 passing yards and a touchdown. Jonathan Taylor was a force on the ground, rushing for 165 yards, while Cam Bynum contributed defensively with an interception.

The Colts’ offense has been effective, ranking first in rushing yards with Jonathan Taylor’s impressive start. Daniel Jones is also performing well, ranking second in passing yards this season. The Colts’ ability to control the game on the ground and through the air gives them a strong chance to win.

Despite some injuries, the Colts have depth in key positions. Michael Pittman Jr. and Tyler Warren provide reliable targets for Jones. With a solid offensive line and strategic play-calling, the Colts can leverage their strengths to secure another victory.

The Titans Can Win If…

The Tennessee Titans are aiming to bounce back after a tough loss to the Los Angeles Rams, 33-19. In that game, wide receiver Elic Ayomanor stood out with 56 receiving yards and a touchdown. Quarterback Cameron Ward also showed promise with 175 passing yards and a touchdown, avoiding any interceptions.

Despite the loss, the Titans have strengths that can lead them to victory. Their defense ranks 9th in both opponent passing interceptions and fumbles recovered, showing they can create turnovers. On offense, running back Tony Pollard is crucial, ranking 6th in rushing yards this season, which can help control the game tempo.

The Titans will rely on key players to step up in their next game. Cameron Ward is projected to throw for over 212 yards, which can be pivotal against the Colts. With a strong kicking game led by Joey Slye, who has made 8 field goals this season, the Titans have the tools to secure a win at home.

Latest Betting Trends

• The Colts are 2-0 against the spread this season and have covered in six of their last eight overall.
• Tennessee has failed to cover in each of its first two games, largely due to offensive struggles.
• The Colts’ offense has averaged 29.5 points per game in their two wins, while Tennessee is scoring just 16 per contest.
• The under has hit in five of the Titans’ last seven home games.

For updated plays and wagering options, see the NFL picks page and the buy picks section

The Lean

The Colts are favored by 4 points against the Titans. My model projects the Colts to win by a score of 24-17. Given the Colts’ strong recent performance against the spread, especially as favorites, picking the Colts to cover the -4.0 spread is a solid choice.

The total for the game is set at 43.5. My model predicts a combined score of 41 points. Considering both teams’ tendencies to go over in recent games, especially the Titans at home, the over 43.5 is the recommended pick.

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Colts Off to Hot Start

The Indianapolis Colts have come out strong in 2025, starting 2-0 and looking like one of the AFC’s most balanced teams. Quarterback Daniel Jones has revived his career after moving on from the New York Giants, completing 45 of 63 passes for 588 yards with two touchdowns and no interceptions. His passer rating sits at 111.1, reflecting the efficiency of the Colts’ offense.

A big part of that success comes from running back Jonathan Taylor. Fresh off being named AFC Offensive Player of the Week, Taylor rushed for 165 yards in a 29-28 win over the Denver Broncos and is averaging 5.5 yards per carry this season. His presence makes the Colts’ offense especially difficult to defend. Fans can follow more on both teams and divisional races at the NFL teams page

Titans’ Offensive Line Struggles

The Tennessee Titans enter this matchup at 0-2, with their biggest concern being pass protection. Rookie quarterback Cam Ward has already been sacked 11 times, the most of any team in the league. While some of the blame lies with Ward holding the ball too long, the offensive line has broken down too often.

With right tackle JC Latham (hip) and right guard Kevin Zeitler (biceps) potentially out again, Tennessee may need to rely on backups John Ojukwu and Oli Udoh. That makes establishing the run game behind Tony Pollard even more crucial. Pollard is coming off a 92-yard outing against the Los Angeles Rams, and giving him room to operate should open up the offense. Bettors can review all the latest NFL scores and odds ahead of this game.

Cam Ward’s Rookie Development

Ward continues to show flashes of promise despite the rough start. Last week, he went 19 of 33 for 175 yards and threw his first touchdown on an improvisational play that highlighted his athleticism. Colts defensive coordinator Lou Anarumo praised Ward’s ability to adapt, noting that his feel for the game is improving each week.

For the Titans to notch their first win, they must give Ward a cleaner pocket and lean on Pollard’s ground production. Those interested in more in-depth analysis should check the NFL previews and matchup breakdowns.

Key Injuries to Watch

The Colts also have some injury concerns. Tight end Tyler Warren (toe), their receptions leader, and wide receiver Josh Downs (ankle) both missed practice during the week. For Tennessee, defensive starters L’Jarius Sneed (back) and T’Vondre Sweat (ankle) are on the injury report. Sweat, however, has expressed confidence he’ll be ready on Sunday.

Injuries could play a major role in determining the flow of this game, and tracking them is essential for bettors. Insights are available in the expert NFL betting guide

Outlook

The Titans must find a way to protect Cam Ward and establish Tony Pollard if they want to avoid falling to 0-3. Meanwhile, the Colts look to continue their balanced offensive dominance behind Daniel Jones and Jonathan Taylor. With both teams managing injuries, execution in the trenches could decide the outcome.

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