Down by 18 points in the second quarter, Peyton Manning led the Colts on a game-winning, 80-yard drive late in the fourth, for a 38-34 win on Sunday.
Manning, who threw for 349 yards and one touchdown, led the biggest comeback in conference title-game history.
Tom Brady, who has led New England to 24 comeback victories in the fourth quarter, was picked off by Marlin Jackson with 16 seconds left in the game.
Indianapolis Colts linebacker Keith O'Neil (53) helped hold Patriots wideout Troy Brown to 32 yards.
New England Patriots wide receiver Reche Caldwell can't haul in a fourth quarter pass in the end zone against Colts cornerback Kelvin Hayden.
Lineman Jeff Saturday (63) scored by jumping on a Dominic Rhodes fumble near the goal line early in the fourth quarter.
Rookie runningback Joseph Addai capped the final drive with the winning score, a 3-yard run with less than a minute left.
Adam Vinatieri's three field goals helped keep the Colts in the game.
In two weeks Tony Dungy will match wits against his former assistant, Chicago's Lovie Smith, in the first Super Bowl to feature African-American head coaches.