The Colts coughed up an early 14-0 lead and trailed 17-14 with 5:20 left in the game when Luck scrambled into the end zone on a third-down play, boosting the Colts (1-0) to a season-opening win.
Luck connected on touchdown passes to Reggie Wayne and Dwayne Allen while going 18-of-23 through the air for 178 yards. He hooked up with Wayne eight times for 96 yards and the score.
Vick Ballard led the Colts' ground game with 63 rushing yards.
Terrelle Pryor was 19-of-29 passing for 217 yards and set a Raiders (0-1) quarterback record with 112 rushing yards in his second career start.