Quarterback Marcus Mariota accounted for both Tennessee touchdowns, snapping a tie with three seconds left in the third quarter when he found tight end Delanie Walker for a 24-yard scoring strike over the middle.
That completed an 80-yard drive that saw the Titans (8-4) convert a fourth-and-1 at the Houston 27 on a 3-yard run by Derrick Henry right before Mariota's touchdown pass.
Ka'imi Fairbairn, who missed two field goals earlier in the game, converted from 42 yards out with 4:37 left in the game to pull the Texans (4-8) within four points. But their chance to win ended when cornerback LeShaun Sims picked off Tom Savage in the end zone with 1:08 remaining.
Henry salted the game away with a 75-yard touchdown run down the left sideline with 46 seconds remaining, giving him 109 yards on 11 attempts.
Houston started the scoring with Fairbairn's 23-yard field goal at the 9:21 mark of the first quarter. The drive was a result of a fumbled punt return by Adoree' Jackson that the Texans' Jordan Todman recovered at the Tennessee 41.
Tom Savage's 4-yard touchdown pass to Stephen Anderson with 10:40 remaining in the first half gave Houston a 10-point lead. It finished an 87-yard drive that featured a 57-yard completion from Savage to Braxton Miller as the Titans blew a coverage.
Mariota drew Tennessee within 10-7 with 4:18 left in the half on a 9-yard touchdown run, finishing off a 75-yard drive that was keyed by Henry's 24-yard burst off right tackle.
Fairbairn clanged a 48-yard attempt off the left upright with 43 seconds remaining in the half, the first time an opponent has missed a field goal in 26 attempts against the Titans this year. Tennessee managed to drive into field-goal range and Ryan Succop converted from 43 yards out with three seconds left in the half for a 10-10 tie.
Savage finished the day 31-of-49 passing for 365 yards and the interception, his 13th turnover in seven games.
Mariota was 15 of 23 for 150 yards.
NOTES: Tennessee deactivated WR Rishard Matthews (hamstring) for the second straight game, with veteran Eric Decker drawing the start in his place. ... Other inactives for the Titans were QB Brandon Weeden, CB Kalan Reed, DB Curtis Riley, FB Jalston Fowler, G/C Corey Levin and DE David King. ... Houston inactives were WRs Will Fuller V (ribs) and Cobi Hamilton, OLBs LaTroy Lewis and Brennan Scarlett (foot), G Kyle Fuller, T Julien Davenport (shoulder) and NT Chunky Clements.