The Broncos entered halftime down to the Eagles, 10-7, but the third quarter was all Manning's, throwing three touchdown passes and only one incompletion, USA Today reported.
Sunday's totals brought Manning to 16 touchdowns and zero interceptions this season, setting the NFL record for the most touchdowns through four games.
That wasn't the only record he broke Sunday. Manning surpassed Milt Plum for the longest streak without an interception in NFL history.
The team also set a franchise record for most points in a single game, scoring more than 50 points for the first time since 1963.
Sunday was the Eagles' third-consecutive loss.