Jacoby Brissett threw four touchdown passes as the Colts held off the Texans 30-23 to take over first place in the AFC South.
Indianapolis improved to 4-2, while the Texans fell to 4-3.
Frank Reich now is 3-1 against Bill O’Brien with the only loss coming when the Colts coach refused to accept a tie in overtime.
Brissett had a field day against the Texans’ depleted secondary, completing 26 of 39 passes for 326 yards. Zach Pascal had six catches for 106 yards and two touchdowns, and Texans’ killer T.Y. Hilton caught six passes for 74 yards and a score.
The Texans stayed in it until late, forcing Colts punts on four consecutive possessions. But Houston had two second half drives end in interceptions, another on downs and a fourth on an intentional safety.
Watson finished 23-of-34 for 308 yards with a touchdown and two interceptions.
The Texans had 391 yards but couldn’t get into the end zone from the red zone. All three of their first half field goals came after Houston get inside the Colts 20-yard line.
But injuries to the secondary were the most costly.
Xavier Crawford, a sixth-round choice from Central Michigan, ended the game at corner for Houston.