Houston (2-0) trailed 24-16 late in the fourth quarter but Schaub marched them 87 yards in the final 3 minutes, setting up a TD run by Arian Foster to produce a tie.
On the Texans' final possession in regulation, Schaub (26-for-48 passing, 298 yards, three touchdowns, two interceptions) got Houston within field goal range but Randy Bullock's 46-yard attempt hit the upright.
In overtime, the Texans' signal-caller found Hopkins on a 25-yard completion to the Tennessee 1-yard line, then hit him again two downs later for the game-winning score.
Hopkins finished with seven catches for 117 yards and a score.
Jake Locker was held to 17-of-30 through the air for 148 yards and two touchdowns fir the Titans (1-1).