The Denver Broncos scored more points than they ever had in their 54-year history on Sunday, blowing out the Eagles 52-20 behind Manning's four touchdown throws and two special teams scores.
With two TD passes each to Demaryius Thomas and Wes Welker, Manning completed all but a-half dozen of his 34 throws for 327 yards. He didn't even step on the field in the fourth quarter and cooled his cleats on the sideline for a 12-minute stretch in the first half, too.
Just another day in the life of Manning, whose 16 TD passes are the most in the first month of a season, besting the previous mark of 14 set by Don Meredith in 1966 and tied by Kurt Warner in 1999. Manning also joined Milt Plum in 1960 as the only quarterbacks to throw that many touchdown passes without an interception.
In a game billed as a warp-speed matchup between teams that like to snap the ball quickly, Manning got off to a rather slow start but drove the Broncos (4-0) on a trio of long touchdown drives in the third quarter to make this one another laugher.
The Eagles also (1-3) surrendered two TDs on special teams in losing for the third straight time, all to AFC West opponents: Trindon Holliday's 105-yard kickoff return and Steven Johnson's blocked punt, which he scooped up himself and returned for a 17-yard score.
Matt Prater's 53-yard field goal capped Denver's 15th straight regular season win, which bested the franchise mark of 14 set in 1997-98 and also broke the previous franchise scoring record of 50 points set against San Diego on Oct. 6, 1963.
Only the 1966 Dallas Cowboys, with 183 points, scored more than the Broncos' 179 in their first four games.
Holliday, the former NCAA track champion who has run sub-10-second 100-meter dashes, tied his own franchise record with a 105-yard touchdown return on a kickoff in the first half. It was his sixth TD return in 21 career games.
It oddly worked in Philadelphia's favor, keeping Manning on the sideline for more than 12 minutes on the game clock, and Michael Vick capitalized on a tiring Denver defense to keep it close - for a while.
The Broncos led 21-13 at halftime.
After throwing a 6-yard scoring pass to Welker, Manning stood impatiently on the sideline for the final 10:19 of the first quarter and the first 42 seconds of the second quarter, and when he did get the ball back, his 40-yard pass went off a wide-open Eric Decker's fingertips.
Then, Welker slipped on a third-down screen and Manning was back on the sideline watching Chris Polk's 4-yard touchdown run cut it to 14-13.
The Broncos decided to give their defense a rest and ran the ball seven times on their next drive, which ended with Knowshon Moreno bullying his way into the end zone from 4 yards out. Moreno's frustration foul killed another promising drive in the final minute of the first half.
Holliday's TD return was the sixth of his short 21-game career, counting playoffs. His rate of one TD per every 3.5 games played is the best since the 1970 AFL-NFL merger.
It was sandwiched around chip-shot field goals by Alex Henery after stalled Philly drives.
Philadelphia came into the game with just one three-out-and in 38 drives and promptly produced its second, after which Manning drove the Broncos 74 yards in nine plays for the touchdown.
Vick finished 14 of 27 for 248 yards with no touchdowns and no interceptions and ran eight times for 41 yards.