Locker's score erased a 10-7 deficit the Titans (5-9) took advantage of five Jets turnovers in logging only their second victory in seven games.
The Titans quarterback finished 13-of-22 through the air for 149 yards with no turnovers and Chris Johnson amassed 122 yards with a score on 21 carries in Tennessee's win.
The Jets (6-8) had a chance to pull out a victory on their final possession after the Titans' Brett Kern shanked a punt from his own end zone and New York took over at the Tennessee 25-yard line with 47 seconds left.
But New York quarterback Mark Sanchez couldn't handle a low snap and fumbled the ball, with Zach Brown recovering it to end the threat.
Sanchez was picked off four times, completing 13-of-28 passes for 131 yards as the Jets saw their two-game winning streak snapped.