NASHVILLE, Tenn. -- Staring at their first 0-3 start since 2011, the Indianapolis Colts desperately needed a victory.
And Andrew Luck led the way.
The Colts' quarterback made sure Titans rookie Marcus Mariota will have to wait for his turn at a big win in this AFC South rivalry.
"This win was big," Luck said. "That's a good Tennessee team, it's in the division, it's on the road. If this can jumpstart a hot streak, then that's what we need."
The Colts (1-2) trailed 27-14 before Luck got going, and Luck improved to 7-0 against Tennessee with another stunning comeback.
He drove the Colts 98 yards before hitting Phillip Dorsett on a 35-yard TD with 6:49 left to make it 27-21.
Dwight Lowery became the first defender to intercept Mariota with a 69-yard interception return for a touchdown in the second quarter. He picked off Mariota again to give the ball back to Luck.
Luck found Donte Moncrief for an 11-yard TD for a 28-27 lead just 56 seconds later.
The Titans (1-2) have lost 13 of 14 against their AFC South foe.
"This one hurts, because we had it," Titans linebacker Brian Orakpo said. "This was the defending AFC South champs, and we definitely had this game. There were some positives to take from this game, but we're not into moral victories."
Trailing 35-27, Mariota drove the Titans for a TD to make it 35-33 and the chance to tie the game inside the final minute.
Defensive pass interference put the ball at the 1 for a closer chance at the 2-point conversion, but rookie fullback Jalston Fowler was stopped for a big loss.
Tennessee's onside kick went out of bounds, allowing the Colts to kneel down for their first win after a rocky start for a team that was in the AFC championship game last season.
"This one was one for the ages, as far as I'm concerned," Colts coach Chuck Pagano said.
Frank Gore ran for two TDs, including the clincher on a 6-yard run with 2:51 left.
Mariota looked ready to make his first home game something for the record books. He threw two TDs, tying Mark Rypien as the only quarterbacks to throw eight touchdown passes in his first three games. Rypien had his eight TD passes in 1988 for Washington.
The rookie threw for a franchise-record 367 yards, and Tennessee outgained the Colts 433-378 after holding the ball for nearly 35 minutes.
After trailing 14-0 in the second quarter, the Titans scored 27 straight points in taking a 27-14 lead.
The Colts sacked the rookie three times, and Mariota has lost two straight games.
The Heisman Trophy winner from Oregon said he couldn't remember the last time he lost consecutive games.
"It's been a while for sure," Mariota said.
Luck came in with a league-high five interceptions, and he attempted a career-low eight passes in the first half. The Titans also intercepted him twice in the span of 3 minutes in the third quarter.
Off to a slow start for a second consecutive season, the Colts shuffled up their offensive line, deactivating left guard Lance Louis and benching right guard Todd Herremans.
Jack Mewhort moved from right tackle to left guard, and Hugh Thornton started at right guard with Joe Reitz coming off the bench at right tackle.
Copyright 2015 by The Associated Press