Vick went down with a left hamstring late in the second quarter after rushing for a team-high 79 yards on seven carries and passing for 105 more.
Foles took over behind center and, with the Eagles down 21-19 in the third quarter, used a series of New York turnovers to rack up 17 straight points ending the game, including TD tosses to Brent Selek and DeSean Jackson (seven catches, 132 yards).
Foles finished with 197 passing yards on16-of-25 efficiency and Alex Henery went 5-for-5 on field goals as Philadelphia took advantage of four Giants mistakes en route to the win.
Eli Manning compiled 334 passing yards, going 24-of-52 through the air with two TD tosses to Rueben Randle. But he was intercepted three times in final quarter for New York, which is off to its first 0-5 start since 1987.
Hakeem Nicks led the Giants' receivers with 142 yards on nine catches.