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Indianapolis Colts vs Tennessee Titans Prediction 9/21/2025 Today’s NFL Picks

Indianapolis Colts quarterback Daniel Jones (17) hands the ball off to Indianapolis Colts running back Jonathan Taylor (28) on Sunday, Sept. 14, 2025, during a game against the Denver Broncos at Lucas Oil Stadium in Indianapolis.

Indianapolis Colts quarterback Daniel Jones (17) hands the ball off to Indianapolis Colts running back Jonathan Taylor (28) on Sunday, Sept. 14, 2025, during a game against the Denver Broncos at Lucas Oil Stadium in Indianapolis.

Indianapolis (2-0) vs Tennessee (0-2)

September 21, 2025 at 01:00 PM EDT

The Line: Betting Odds: Tennessee +4.5 — Over/Under: +43.5

(Get latest betting odds)

The Indianapolis Colts and the Tennessee Titans meet in week 3 NFL action from Nissan Stadium on Sunday. We will look at this from a betting perspective and determine the best bets for this game. Here’s an Indianapolis Colts vs. Tennessee Titans prediction.

Indianapolis Colts Recap

The Indianapolis Colts come into this game looking to add on to their 29-28 win over the Denver Broncos last time out to sit at 2-0 this season. After this game, the Colts will head on the road for a game against the Los Angeles Rams.

Colts Looking To Remain Unbeaten

Daniel Jones has thrown for 588 yards and 2 touchdowns on 71.4% passing while also rushing for 3 TDs as well this season. Jonathan Taylor has rushed for 236 yards to lead the Colts on the ground while Tyler Warren has a team-high 11 catches for 155 yards and Michael Pittman Jr. has 120 receiving yards and a touchdown. Alec Pierce also has 104 receiving yards as well this season. On defense, Joe Bachie and Nick Cross each have a team-high 13 total tackles while Cam Bynum has a pair of interceptions for the Colts’ defense so far this season. 

Tennessee Titans Recap

The Tennessee Titans come into this game looking to bounce back from a 33-19 loss to the Los Angeles Rams last time out to fall to 0-2 on the year. After this game, the Titans will head on the road for a game against the Houston Texans.

Titans Looking For First W

Cam Ward has thrown for 287 yards and a touchdown on 50.8% passing while Tony Pollard’s rushed for 152 yards so far this season. Calvin Ridley leads the Titans with 7 grabs for 84 yards and Elic Ayomanor also has 69 receiving yards and a touchdown this season. On defense, Jarvis Brownlee Jr. has a team-high 17 total tackles while Tennessee’s defense as a whole has combined for 2 sacks and 3 interceptions so far this season.

Indianapolis Colts @ Tennessee Titans Betting Trends: Week 3

Why the Tennessee Titans will win

  • The home team has won each of the Colts’ last six games.
  • The Colts have lost each of their last six road games following a win.
  • The Colts have failed to cover the spread in each of their last six September games as road favorites.
  • The home team has covered the spread in six of the Colts’ last seven games.
  • The Titans have scored the first touchdown in each of their last four games as home underdogs against AFC opponents.
  • The Titans have won the first quarter in each of their last four games as home underdogs against AFC opponents.
  • The Colts have lost the first half in each of their last seven road games following a home win.

Why the Indianapolis Colts will win

  • The Titans have lost each of their last eight games.
  • The Colts have won each of their last nine games as favorites against AFC opponents.
  • The Titans have failed to cover the spread in each of their last nine home games.
  • The Colts have covered the spread in each of their last six September games against AFC opponents.
  • The Colts have scored the first touchdown in each of their last six road games against AFC opponents.
  • The Colts have won the first quarter in each of their last four road games against AFC opponents.
  • The Titans have lost the first half in each of their last five games against AFC opponents.

Total Points Facts

  • Each of the Colts’ last seven September games as favorites have gone UNDER the total points line.
  • Each of the Titans’ last four games as home underdogs against the Colts have gone OVER the total points line.

Tennessee Titans Player Prop Facts

  • Tyler Lockett has recorded 30+ receiving yards in each of his nine previous appearances against AFC South opponents.
  • Tony Pollard has recorded 89+ rushing and receiving yards in each of his last seven September appearances with his team as an underdog.
  • Tyjae Spears has scored at least one touchdown in each of his last three appearances following a home loss.
  • Heading into Week 3, Joey Slye ranks T1st in the NFL in 50+ yard field goals made (3) this season.

Indianapolis Colts Player Prop Facts

  • Jonathan Taylor has recorded 91+ rushing yards in eight of his last nine appearances with the Colts as favorites.
  • Daniel Jones has recorded 236+ passing yards in each of his last four September appearances.
  • Jonathan Taylor has scored at least one touchdown in nine of his last 10 appearances with the Colts as favorites against teams with a losing record.
  • Michael Pittman Jr. has scored the last touchdown in each of his last three appearances with the Colts as road favorites against AFC South opponents.
  • Michael Pittman Jr. has recorded 63+ receiving yards in each of the Colts’ last seven games as favorites following a win.
  • Jonathan Taylor has recorded 111+ rushing and receiving yards in five of the Colts’ last six games.
  • Daniel Jones has recorded 22+ completions in each of his last six appearances following a win.
  • Heading into Week 3, Jonathan Taylor ranks 1st in the NFL in rushing yards (236) this season.

Matchup/League Facts

  • Titans – one different players have recorded 80+ rushing yards in a game this season – equal-most in the NFL, heading into Week 3.
  • Titans – one different players have recorded 90+ rushing yards in a game this season – equal-most in the NFL, heading into Week 3.
  • Colts – one different players have recorded 80+ rushing yards in a game this season – equal-most in the NFL, heading into Week 3.
  • Colts – one different players have recorded 90+ rushing yards in a game this season – equal-most in the NFL, heading into Week 3.

Indianapolis Colts vs. Tennessee Titans Prediction

I’m on the Titans and the points here. I’d be lying if I said the Colts start to the year wasn’t surprising given that it’s Daniel Jones as the starting QB in Indy, but the fact of the matter is that I’m not ready to buy what the Colts are selling because I have history knowing what Daniel Jones is and I’m just waiting for him to turn back into a pumpkin. The Titans are a team I think that will be at their best at home this season and I think Cam Ward is only going to get better with time and underdogs in this division have been money going back some time now. I’ll side with the Titans and the points here.

Chris Ruffolo's Pick: Tennessee +4.5

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