The Giants (2-1) scored 14 straight points in the fourth quarter to put the contest away after Philadelphia had earlier scored 16 consecutive points to take the lead.
But the Eagles' Vick gave way to back-up Mike Kafka for the second week in a row after suffering a likely broken (non-throwing) hand on a hard hit by Chris Canty.
Kafka was picked off with 8:07 left in the game on a deep sidelines pass with the Eagles trailing 22-16.
Notable deaths of 2014 [PHOTOS]
Michael Sam cut from the Dallas Cowboys