AP photo by Mark Zaleski / Tennessee Titans running back Derrick Henry carries the ball during Sunday's home against the Indianapolis Colts. Henry rushed for 113 yards, and the Titans won 25-16 against their AFC South Division rivals despite having three turnovers and no takeaways.

NASHVILLE — The Tennessee Titans know it's almost impossible to win an NFL game turning the ball over three times.

Somehow, they found a way to overcome their mistakes for a big victory against a familiar foe they have often struggled to beat, especially in Nashville.

Ryan Tannehill threw for 197 yards and three touchdowns Sunday as the Titans held off the Indianapolis Colts 25-16 to grab an early tiebreaker in the AFC South standings. Tennessee triumphed despite Tannehill's two interceptions and a fumble by wide receiver Nick Westbrook-Ikhine.

"I'll take a win no matter what," said Tannehill, whose two picks were turned into 10 points by the Indianapolis offense. "Find a way to win. Obviously have some things to clean up, but we found a way to win, and that's why we're here."

The road team had won the previous five games in this division rivalry, with the Titans only 8-16 in Nashville in the series. This was their first home win over the Colts since Oct. 16, 2017. Tennessee also hadn't won a game with three turnovers since beating the Atlanta Falcons 20-13 on Oct. 7, 2007.

This time, though, the Titans (2-1) are the reigning AFC South champs with the NFL's back-to-back season rushing leader. Derrick Henry ran for 113 yards, topping the 100-yard mark for a sixth straight division game.

Indianapolis coach Frank Reich called it a "heartbreaking loss."

"You don't lose many games when you win the turnovers 3-0," he said.

The Colts (0-3) are off to their worst start since 2011.

"It just feels like a bad dream, honestly," Colts linebacker Darius Leonard said. "Starting 0-3, first loss here in Tennessee. It just sucks. Got to find a way to win."

Carson Wentz started at quarterback for Indianapolis after being questionable with two sprained ankles. He never ran against the Titans, choosing to throw the ball away repeatedly when pressured, and finished 19-of-37 passing for 194 yards while being sacked twice.

Reich said he never thought of giving Wentz a week or two to heal, though it was a game-time decision on whether the quarterback would start. Reich said Wentz's injuries did affect play calls a bit, with the quarterback understanding his limitations.

"We felt like him at 70% or 8% whatever he is, is our best option to beat a very good football team on the road," Reich said.

The Colts twice had first-and-goal inside the 9 in the second half, but Tennessee's defense — much maligned in 2020 — held the Colts to a pair of field goals by Rodrigo Blankenship, the second a 24-yarder with 10:20 left that pulled the visitors within 22-16. Tennessee then put the game away, going on a 14-play drive that chewed up 7:22 of game clock and finished with Randy Bullock's 32-yard field goal.

The Colts tried for a final score, but Blankenship's 51-yard field-goal attempt was wide right with 57 seconds left. The Titans knelt down for the win.

"For the defense to be playing good in the red zone and force a lot of field goals and let them only score one touchdown, I think that was pretty strong," Titans safety Kevin Byard said. "Definitely encouraging. We're 1-0 in the division, so it's a great day."

The Titans had plenty of opportunities to blow the game open but led only 14-10 at halftime because of the interceptions. Darius Leonard picked off Tannehill to set up a 9-yard touchdown run by Nyheim Hines, Kenny Moore II had the second pick, and Blankenship kicked a 43-yard field goal as the first half expired.

Tannehill threw a 6-yard touchdown pass to Chester Rogers against his old team and found Westbrook-Ikhine for an 18-yard touchdown, the first of the 24-year-old receiver's NFL career. Henry also caught a pass from Tannehill under pressure and finished off a 14-yard play with Leonard bouncing off him in the second quarter.

Tennessee linebacker Ola Adeniyi, who had a key sack in overtime during a road win against the Seattle Seahawks a week earlier, finished with 1.5 sacks against Indianapolis.