Joseph Addai ran for 171 yards and tied a franchise record with four touchdowns for the Colts. Only Lenny Moore, Lydell Mitchell and Eric Dickerson had scored four in a game.
With a win next week against Tennessee, the Colts clinch the AFC South.
Addai scored on the Colts' first three series. The second came after Reggie Wayne's 36-yard one-handed catch.
Peyton Manning became the fastest to 3,000 completions, according to the Elias Sports Bureau, 139 games, seven fewer than Dan Marino and Drew Bledsoe.
The only good news for the Eagles was Brian Westbrook's 124 rushing yards. He is the first Eagle since Wilbert Montgomery in 1981 with three consecutive 100-yard games.
NOTABLE: Colts tight end Dallas Clark sprained his right knee while being tackled in the second quarter and did not return. His status is unknown.