Luck picked up 191 aerial yards, completing 14-of-28 passes for the Colts (11-5), who claimed a victory as Pagano returned to the bench for the first time since Week 3 after battling leukemia.
Indianapolis -- which improved to 11-0 all-time at home against the Texans -- earlier secured an AFC wild card berth after going 9-4 under interim Coach Bruce Arians.
AFC South champion Houston (12-4), meanwhile, missed a chance to lock in home field advantage throughout the playoffs after closing the regular season with three losses in four games.
Andre Johnson led the Texans' receiving corps with 141 yards on 12 catches.
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