DKNetwork Logo DKNetwork Logo
Tennessee Titans vs. Indianapolis Colts prediction, pick for NFL Week 3 on Sunday 9/21/25

Tennessee Titans vs. Indianapolis Colts prediction, pick for NFL Week 3 on Sunday 9/21/25

Published:

By: Alex Hunter

The Titans are hosting the Colts on Sunday for Week 3. On DraftKings Sportsbook, Indianapolis is favored by 4.5 points and this game carries a total of 43.5 points.

Below, I’ll break down this matchup between the Titans and Colts and give a pick for the game.

Titans vs. Colts prediction, pick

The Titans have gotten off to a poor 0-2 start this season, while the Colts have been one of the NFL’s biggest surprises with a 2-0 record. While its still early, Cam Ward has struggled for Tennessee. The No. 1 pick out of Miami has yet to eclipse 200 passing yards and Ward has only thrown for one touchdown. The quarterback is completing just 50.4% of his passes and he is averaging a pathetic 4.7 YPA, both of which rank dead-last among all quarterbacks. Ward hasn’t thrown a pick despite his passing inefficiencies, but he has unfortunately lost two fumbles.

Ward still has plenty of time to turn his rookie season around, but there’s no denying that his start has been far from ideal and the Titans’ defense hasn’t been great, either, ranking 20th in defensive EPA. Tennessee has been shredded on the ground, giving up the third-most yards per rush (5.5), which is a terrible sign with the Colts and Jonathan Taylor up next.

Taylor is the NFL’s leading rusher (236) and he is averaging 5.5 YPC. On top of Taylor thriving, Daniel Jones has been masterful at quarterback for Indianapolis. The veteran is leading all quarterbacks in YPA (9.3) and he has thrown for two touchdowns to no interceptions. Jones also been active on the ground with three rushing touchdowns, which is tied for the most among quarterbacks. Combine Jones and Taylor’s efforts, and the Colts rank second in offensive EPA, trailing only the Ravens.

Indianapolis’ defense hasn’t been much better than the Titans, ranking 19th in defensive EPA, so this could be a spot for Ward and Tennessee’s offense to come alive. That being said, this such a great spot for the Colts’ offense, especially on the ground, that it’s hard to envision the Titans scoring enough points to keep pace with this red-hot Indianapolis team, regardless of the fact that this game is in Tennessee.

Titans vs. Colts pick, best bet

The Colts struggling in this spot is unlikely and their excellent start to the season should continue with a win over the struggling Titans. While Indianapolis -4.5 is a strong bet, backing the Colts for over their team total of 23.5 points (-120) is a safer wager.

As noted above, Indianapolis ranks second in offensive EPA and the team has scored 33 and 29 points, respectively, in its first two games.

Best Bet: Colts Over 23.5 Points (-120)

Alex Hunter is an avid DFS player and sports handicapper, who has been a proud member of the DraftKings Network team since 2020. He is a data-driven analyst, who earned his bachelor’s degree in communications at Worcester State University and has been in the sports content business for nearly a decade, covering the NBA, NFL and PGA TOUR. Alex is a diehard Boston Celtics fan, who loves to be on the golf course when he isn’t grinding lineups or producing content. For all of Alex’s work or if you need any lineup advice, be sure to follow him @Hunta512 on X.
Disclaimer

I am a promoter at DraftKings and am also an avid fan and user (my username is Hunta512) and may sometimes play on my personal account in the games that I offer advice on. Although I have expressed my personal view on the games and strategies above, they do not necessarily reflect the view(s) of DraftKings and do not constitute a representation that any particular strategy will guarantee success. All customers should use their own skills and judgment in building lineups. I may also deploy different players and strategies than what I recommend above. I am not an employee of DraftKings and do not have access to any non-public information.