Manning threw four touchdowns - all to tight ends with Larry Donnell catching three passes in the end zone, while the quarterback also rushed for a touchdown of his own.
Washington quarterback Kirk Cousins didn't enjoy his night anywhere near as much as he threw four interceptions and also fumbled the ball early on.
The Redskins six giveaways on the night led to 31 points for the Giants, and Cousins' three interceptions in a span of five attempts in the third quarter were painful to watch.
New York have now recorded back-to-back victories after a slow start and look to be improving dramatically on offense as they get to grips with new offensive coordinator Ben McAdoo's playbook.
Washington will need to pick themselves up after the heavy defeat, and they look to be in trouble in the NFC East already, with their next game against the reigning Super Bowl champions the Seattle Seahawks.