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.