Indianapolis Colts vs Tennessee Titans Prediction, 9/21/2025 NFL Picks, Best Bets & Odds Week 3

Game: Indianapolis Colts vs Tennessee Titans

Date: Sunday, September 21, 2025

Location: Nissan Stadium in Nashville, TN

TV: CBS

Odds-Point Spread: Titans (+3.5)

Total-Over-Under: 43.5

Nissan Stadium is the place where the Tennessee Titans (0-2) will try to beat the Indianapolis Colts (2-0) on Sunday. Indianapolis opens as 3.5-point favorites. The total comes in at 43.5.

The Indianapolis Colts step onto the field holding a record of 2-0 over the course of this season. In their last game, the Colts played against the Denver Broncos and earned the victory with a final of 29-28. Jonathan Taylor led the offense in rushing for the Colts with 25 totes for 165 yds (6.6 yards per attempt). Tyler Warren had an average of 19.8 yds per reception by accumulating 79 yds on 4 receptions. Daniel Jones went 23-34 with 316 yds passing and 1 touchdown. He had a QB rate of 107 and finished the game without throwing a pick. In the running game, the Colts gave up 118 yds on 24 tries, which averages out to 4.9 yards per rush allowed. Indianapolis relinquished 22 pass completions on 30 attempts for a total of 206 yards, and a completion rate of 73.3%. On the day, they tallied 66 plays which gave them 473 yards. The Indianapolis Colts ran the rock 32 times and amassed 167 yds, which earned them an average of 5.2 yards per tote.

The Colts have recorded 891 yards over the course of this year. Indianapolis has notched 30 1st downs as a team, and they have committed 15 infractions for 113 yds. When you look at notching touchdowns, Indianapolis has notched 2 touchdowns via the pass and 3 rushing touchdowns. They have yet to give the ball away. As a unit, they are sitting at 161.5 rushing yds which has them sitting 3rd in the league. When examining scoring, the group who plays in Indianapolis average 31.0 PPG.

When analyzing passing yds, the Colts have granted 339 yds, which has them sitting 7th in the league. They have allowed 169.5 yards per contest by way of the pass, and are allowing a completion% of 67.2%. On the whole, they have allowed 196 rushing yards through 2 contests on the season. They have allowed 4 touchdowns via the pass, and 1 touchdown via the ground game. Overall, they are conceding 267.5 total yards per outing, which has them ranked 5th in the NFL. They are allowing an average of 5.4 yds per tote and 98.0 rush yards per game over the course of the season. The Colts are 11th in professional football if you're looking at the other team scoring points, granting 18.0 points per outing.

Get all of our NFL Picks

The Titans head into this matchup 0-2 this season. In their last contest, the Titans took a loss by a score of 33-19 against the Los Angeles Rams. Tony Pollard ran the football 20 times for 92 yds, ending the game with 4.6 yards per attempt for Tennessee. Calvin Ridley was featured in the passing game for the Titans, bringing in 3 balls for 57 yds (19.0 yards per reception). Cam Ward (1 TD) ended the contest with 175 yds on 19-33 through the air while his quarterback rate was 82.3. He didn't toss any interceptions and his Y-A was 5.3 yds. Tennessee relinquished 25 run attempts for 149 yards (6.0 yards per carry). The Titans passing defense gave up a completion percentage of 69.7%, relinquishing 290 yards on 23 out of 33 passing. The Titans finished the game with a total of 252 yds while they ran 59 plays (4.3 yds per play). Tennessee ran for 4.2 yards per tote, totaling 109 yards on 26 carries.

If you examine how much they score, the Titans are 30th in professional football, holding an average of 15.5 points per outing. This year, the Titans have a total of 205 yards through the air and are sitting at 102.5 yards through the air per outing, which has them ranked 32nd in the NFL. They hold an average of 90.0 running yds per outing, and have carried the football for 180 total yards. The Tennessee Titans maintain an average of 192.5 yards per contest, which is 32nd in professional football. The Tennessee offense has conceded 193 yds by way of 23 infractions, which has them sitting 1st in the league if you're looking at hurting your team. They have recorded 15 first downs offensively.

They have allowed 3 touchdowns through the air plus 228.0 yards via the pass per outing, putting them 20th in pro football. Tennessee has relinquished a total of 300 rushing yards (150.0 yards per contest), in addition to 3 touchdowns on the ground over the course of this season. Their defense currently has 5 takeaways. Overall, they have conceded 53 pts. The Titans defense has participated in 130 plays, which has them ranked 27th in the NFL. The Titans are giving up 26.5 points per contest, ranking them 23rd in the NFL.

Who will win tonight's Colts-Titans NFL game against the spread?

Josh's Pick: Take the Colts -3.5

Get $60 worth of FREE premium member picks. No Obligation. No Salesman. No Credit Card. Fast Sign up with Instant Access Click Here