Indianapolis Colts vs Tennessee Titans Picks and Predictions for Sunday, September 21, 2025

By: David Anicetti Updated 09/19/2025, 03:13 PM ET

The Indianapolis Colts (2–0) visit the Tennessee Titans (0–2) at Nissan Stadium in Nashville on Sunday at 1:00 PM ET on CBS. The Colts edged Denver 29–28 last week, while the Titans lost 33–19 to the Rams. The current odds are Colts -3.5 (-105), Titans +3.5 (-115), total 43.5 (over -105, under -115), with moneylines Colts -185 and Titans +155. Tap into the psychology of success this NFL season with expert strategies that lead to winning free NFL picks.

Indianapolis Colts Preview

The Colts are off to a strong start. Daniel Jones has thrown for 588 yards, completing 71% of his passes with two touchdowns and no interceptions. Jones’ favorite targets have been Tyler Warren, who leads the team with 155 receiving yards, and Michael Pittman Jr., who has 120 yards and a TD reception. Spencer Shrader is 9-for-9 on field goals.

Jonathan Taylor continues to drive the offense with 236 rushing yards on 43 carries. His steady production opens passing lanes and keeps defenses on their heels. On defense, the unit has three sacks and two interceptions, with Cam Bynum already recording two picks. Indianapolis has scored 62 points across two games and is off to a strong start.

Tennessee Titans Preview

Tennessee is looking to avoid a 0-3 start. Rookie quarterback Cam Ward has 287 passing yards with one touchdown, but has been sacked 11 times. The passing attack has lacked strength, though Calvin Ridley and Elic Ayomanor have been reliable targets, combining for 153 yards and a score.

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Tony Pollard leads the running game with 152 yards on 38 attempts. Pollard gives the Titans a chance to control tempo, but the offense needs more consistent blocking. Defensively, Jeffery Simmons has produced pressure up front, and the secondary has one interception, but extended drives against them have worn the unit down, which has resulted in giving up points in the fourth quarter.

Indianapolis vs Tennessee Prediction

The Colts hold the advantage with a steadier passing game and stronger running attack. Tennessee’s protection issues are a poor matchup against a Colts defense that has pressured the passer in both games this season. Pollard may keep the Titans close early, but Indianapolis should pull away late. Final Score Prediction: Indianapolis Colts win and cover ATS 23-13.