Manning's TD tosses gave him a total of 16 for the season -- the most ever after after four games in NFL history -- as the Broncos set a club mark for most points scored in a single game.
The 37-year-old signal-caller completed 28-of-34 passes for 327 yards and has yet to throw an interception for Denver (4-0).
Demaryius Thomas and Wes Welker each made two scoring grabs and Knowshon Moreno ran for 78 yards and a touchdown on 12 carries in the win -- a club-record 15th straight regular-season triumph for the Broncos.
The Eagles (1-3) dropped a third straight as Michael Vick was held without a TD pass. He finished 14-of-27 for 248 passing yards.
Backup Nick Foles found Jeff Maehl on a fourth-quarter touchdown pass for Philadelphia.