Colts quarterback Andrew Luck, who replaced Manning after he was released in March of 2012, accounted for four Colts touchdowns; three through the air and one rushing. Luck was 21-38 for 228 yards and 3 touchdowns, and rushed for a fourth.
Indianapolis built a 33-17 lead heading into the fourth quarter due in part to their defense befuddling Peyton Manning, who was sacked twice in the game by former teammate Robert Mathis. But, as is often the case, Manning came storming back in the fourth quarter, leading Denver to 16 points.
In the end, mistakes, penalties, and turnovers did Denver in. The Broncos had four turnovers on the night, including a Manning interception in the fourth quarter, and a sack-fumble for a safety in the first half.
The loss gives the Colts (5-2) are firm three-game lead in the AFC South, while Broncos (6-1) fall to second place in the AFC West behind the undefeated Chiefs (7-0). Manning finished the night with 386 yards passing, 3 touchdowns, one pick, and a fumble.