In the stunning comeback, quarterback Peyton Manning threw two touchdown passes sandwiching Gary Brackett's 68-yard touchdown fumble return.
Manning completed 25-of-34 passes for 247 yards with one interception.
Joseph Addai scored once on 17 carries for 71 yards, while Marlon Jackson and Melvin Bullit combined to lead the defense with 21 combined tackles for the Colts (2-2), who have won 12 of their last 13 contests against the winless Texans (0-4).
Houston's Sage Rosenfels, subbing for ill starting quarterback Matt Schaub, completed 21-of-33 passes for 246 yards, one touchdown and one interception.
Schaub spent Saturday night in the hospital with a virus, but was active for the game.
Receiver Andre Johnson scored once after nine catches for 131 yards.
Rookie Steve Slayton scored twice on 16 carries for 93 yards, and Kris Brown kicked two field goals.