Colts vs. Titans 2025 Prediction, Odds, Picks - Sep 21

The Indianapolis Colts (2-0) and Tennessee Titans (0-2) will play each other in a matchup of two division rivals. The Colts are the favorites, expected to win by at least a field goal but less than a touchdown (currently -5.5). The game has an over/under of 43.5 points.

Keep up with the 2025 NFL season on FOX Sports.

Patrick Mahomes, Chiefs still contenders after rough start? Can other 0-2 teams turn season around?

Drew Brees joined the "FOX NFL Kickoff" crew to discuss whether the Kansas City Chiefs can bounce back after an 0-2 start and which other 0-2 teams can turn their season around.

Colts vs. Titans Odds & Betting Lines

Colts vs. Titans Prediction & Pick

• Pick ATS: Titans (+5.5)
  
• Pick OU: Over (43.5)
  
• Prediction: Colts 25 - Titans 21

How to Watch Indianapolis vs. Tennessee

• Game date: Sunday, September 21, 2025
• Time: 1 p.m. ET
• Venue: Nissan Stadium
• Location: Nashville, Tennessee
• TV: CBS
• Live Boxscore: FOX Sports

Colts vs. Titans Recent Matchups

• In their last five head-to-head bouts, Indianapolis has beaten Tennessee four times.
• Tennessee has been outscored by 12 points in its last five tilts against Indianapolis.

Indianapolis Betting Info

• Indianapolis has covered the spread every time so far this season.
• Indianapolis games this year have hit the over on one of two set point totals (50%).
• The Colts have been moneyline favorites a single other time this season, a game they won.
• The implied probability for this matchup, considering the moneyline, gives the Colts a 71.0% chance to win.

Colts Stats

Indianapolis' Key Players

Offense

• Daniel Jones has 588 passing yards (third in the NFL), two touchdowns and zero interceptions this year. He has completed 71.4% of his attempts, averaging 294.0 yards per game and 9.3 per attempt.
• In addition to his passing stats, Jones also has 28 rushing yards (third on the Colts), with three rushing touchdowns.
• Jonathan Taylor averages 5.5 yards per carry (sixth in the NFL) and 118.0 yards per game, and has 236 total rushing yards (second in the NFL). He has not yet scored a rushing TD this season.
• He has also caught five passes (on five targets) for 77 receiving yards with one touchdown. He's averaging 38.5 receiving yards and 2.5 catches per game.
• Through two games played, Michael Pittman Jr. is averaging 60.0 yards and 5.0 receptions per game to total 120 receiving yards and 10 catches. He's been targeted 13 times, and has one receiving touchdown.
• Tyler Warren has put up 155 receiving yards without a touchdown with 11 catches on 16 targets. He is averaging 5.5 receptions and 77.5 yards per game.

Defense

• On the defensive side, Nick Cross has 13 tackles, 1.0 TFL, and one sack in 2025. His tackle total leads the Colts.
• Camryn Bynum has seven tackles and two interceptions this season.
• This season, Kenny Moore II has recorded 1.0 sack (first on the Colts) to go with his 1.0 TFL and eight tackles.
• So far this season, DeForest Buckner has nine tackles and 2.0 TFL.

Tennessee Betting Info

• Tennessee has covered the spread once in two games with a set spread.
• This year, the Titans have one ATS win in two games as an underdog of 5.5 points or more.
• Games involving Tennessee have hit the over once this year.
• The Titans have lost both games they've played as underdogs this season.
• Bookmakers have implied with the moneyline set for this matchup that the Titans have a 33.3% chance to win.

Titans Stats

Tennessee's Key Players

Offense

• Tony Pollard has not rushed for a touchdown this year, but has racked up 152 total rushing yards (76.0 per game and 4.0 per carry).
• Pollard's contributions include one catch (0.5 per game) on two targets for 29 yards (14.5 per game), but he has not found the endzone in the passing game.
• Elic Ayomanor has put together a 2025 stat sheet that includes six catches for 69 yards and one receiving touchdown in two games played. He has been on the receiving end of 13 targets and is averaging 3.0 receptions per game.
• In two games this season, Cameron Ward has racked up 287 passing yards, with one touchdown against zero interceptions and completing 50.8% of his passes.
• Calvin Ridley has 84 receiving yards from seven receptions after receiving 14 targets.

Defense

• In 2025, Jeffery Simmons has recorded 1.0 sack to go with 1.0 TFL and six tackles over two games.
• Jarvis Brownlee has 17 tackles, 2.0 TFL, and one pass defended.
• Amani Hooker has 13 tackles, 1.0 TFL, one sack, and one pass defended in the 2025 campaign.
• Cody Barton has 1.0 TFL, 14 tackles, and one interception.

FOX Sports created this story using technology provided by Data Skrive and data from Sportradar.

Want great stories delivered right to your inbox?

Create or log in to your FOX Sports account, follow leagues, teams and players to receive a personalized newsletter daily.

FOLLOW Follow your favorites to personalize your FOX Sports experience

Tennessee Titans

Indianapolis Colts