Andrew Luck threw for three touchdowns and ran for another outplaying predecessor, Peyton Manning, in a 39-33 victory over the Denver Broncos.
The Colts win ended the Broncos' 17-game regular-season winning streak in the first game Manning played against his former team since being released in March 2012.
Peyton threw for 386 yards and three touchdowns with one interception and was sacked four times.
The Broncos drop to 6-1 after losing their first game of the season.
Indianapolis has not lost consecutive games under Luck.