The Eagles (9-4) took over sole possession of first place in the NFC East, a game ahead of Dallas (8-5), which fell 20-17 to the San Diego Chargers.
McNabb gave the Eagles, who have won four straight, an early lead with an 8-yard pass to Brent Celek and later hooked up with DeSean Jackson on a 60-yard scoring play.
Jackson ran a punt back 72 yards for a touchdown and Sheldon Brown had a 60-yard fumble return for another score.
The Eagles also had 1-yard touchdown runs by Michael Vick and Leonard Weaver and a 20-yard David Akers field goal.
McNabb completed 17-of-26 passes for 275 yards and Jackson ended up with six catches for 178 yards.
.Eli Manning threw three scoring passes for the Giants (7-6) on plays that covered 68 yards to Hakeem Nicks, 61 yards to Domenix Hixon and 4 yards to Kevin Boss.
The Giants also scored on runs of 3 yards by Ahmad Bradshaw and 1 yard by Brandon Jacobs and a 26-yard field goal by Lawrence Tynes.
Manning accumulated 391 yards on 27 completions in 38 attempts.
Kate Middleton recycles dress at movie premiere
Couple mistakenly served bag of cash at McDonald's drive-thru