Vince Young, the backup quarterback who 10 victory over the Giants.
The Giants (6-4) received the ball back with 2:45 remaining, but the Philadelphia defense, largely culpable in five fourth-quarter collapses this season, delivered the decisive blow, as Manning fumbled the ball away on a Jason Babin sack.
Young completed 23-of-36 passes for 258 yards, two touchdowns and three interceptions for the Eagles, who halted a two-game slide.
Manning threw for 264 yards with a touchdown and an interception for the Giants, who have dropped two in a row.
Cruz caught six passes for 128 yards, while Brandon Jacobs totaled just 21 yards on 12 rushes to lead the team.