Vick started despite suffering a concussion in last week's 35-31 loss at Atlanta. He left with a broken right hand in the fourth quarter after helping the Eagles overcome a 14-0 first-quarter deficit to take a 16-14 lead.
It's uncertain how long Vick will be out. He'll have a CT scan Monday.
"I don't know anything right now except my hand is broken," Vick said.
"I felt I got hit late. No flag," Vick said. "At some point something catastrophic is gonna happen. Not to blame the refs, but more precautions should be taken. I'm on the ground all the time in the pocket."
Without their Pro Bowl quarterback, the Eagles (1-2) hardly look like the "Dream Team" that entered the season with Super Bowl or bust expectations.
Manning threw a pair of TD passes in the fourth quarter to rally New York. The Giants (2-1) have won two in a row and snapped a six-game losing streak against their division rivals.
"It's always good to beat those guys, especially here," Manning said. "They have good players and we knew we had to come in with the same game plan as last year and just finish it this time."
In their previous meeting at the Meadowlands last December, the Eagles rallied from a 21-point deficit with 8:17 left, and won 38-31 on DeSean Jackson's 65-yard punt return for a touchdown on the last play.
The teams traded a lot of trash talk in the offseason and during the week. The Giants backed it up.
"I think I responded today," Giants safety Antrel Rolle said. "I'm not scared of anyone on the field. I think it's more mental than physical. They tried to get in my head sticking their hands in my face, blocking me after the play, but if they want to fight, I'll fight anyone, but in between the lines, I'm too smart to get thrown out of the game."
Manning threw for 254 yards, and Ahmad Bradshaw ran for 86 and had 53 more receiving, including a TD. Filling in because Mario Manningham and Domenik Hixon are out, Cruz had three catches for 110 yards and his first two career scores.
Aaron Ross, who was benched in the second half of New York's win over St. Louis last Monday, had two interceptions that led to 14 points.
LeSean McCoy had 128 yards rushing and one TD for Philadelphia, which has blown two fourth-quarter leads in consecutive games.
After McCoy was stopped for a 3-yard loss by Michael Boley on fourth-and-1 from the Giants 43, Manning drove New York in for the go-ahead score. He tossed a 28-yard TD pass to a well-covered Cruz to put the Giants up 20-16. Jacobs ran in for the 2-point conversion to make it 22-16.
"It means the world to me because a lot of people were saying our receivers were down and who would step up and I was happy to be that guy that stepped up to help my team," Cruz said.
Mike Kafka replaced Vick on the ensuing possession and Ross intercepted his first pass. Manning connected with Bradshaw for an 18-yard TD pass to put the game away.
Vick finished 16 of 23 for 176 yards and one interception. He ran for 31 yards. Vick looked shaky early, but made a few nice throws before leaving.
He didn't seem all that happy after the Eagles kicked a field goal to pull within 14-13 at halftime. Vick looked angry as he walked off the field, waving his arms and pointing. Jackson tried to calm him down, but Vick didn't seem interested in listening.
"He was just frustrated with the offensive line," Jackson said.
The Eagles dominated time of possession by a nearly 3-1 margin throughout the first three quarters, but didn't take the lead until the final minute of the third when Alex Henery kicked a 21-yard field goal.
It was a disappointing end to a drive that began at the 10 and stalled at the Giants 1. The Eagles had a first down at the 2 and failed on four runs to get it in. McCoy didn't get one of the handoffs.
Philadelphia got a lucky bounce on that drive. Vick ran 8 yards for a first down on third-and-6 from the 14. Vick fumbled at the end of the run, but the ball bounced forward and left tackle Jason Peters caught it in the air. Peters rumbled for 5 more yards.
Vick left the game for X-rays on his right hand after that drive and was temporarily replaced by Kafka. But he returned during a time out while Kafka was in the huddle and played one more drive before going to the bench.
Steve Smith made a crucial mistake on the first ball that came his away against his former team. Smith left the Giants for Philadelphia and returned ahead of schedule from knee surgery to be ready for Week 1. Vick's third-down pass on Philadelphia's first drive hit Smith in the hands and bounced in the air to Ross, who caught it at the Giants 8. Ross returned the interception 19 yards, and Manning needed six plays to lead New York into the end zone.
Rookie linebacker Casey Matthews, who was moved from the middle to the weakside spot earlier in the week, bit badly on a play-fake that allowed Jacobs to get wide open. Manning's perfect throw hit him in stride and the Giants went up 7-0.
Manning connected with Cruz late in the first to give New York a 14-0 lead. Cruz caught a short pass at the Giants 34, but broke Kurt Coleman's tackle and sprinted down the sideline. Cruz again got away from Coleman, when he collided with Asomugha at the Eagles 46, and the second-year pro cruised into the end zone for his first career score.
After the Giants turned it over on downs at the Eagles 29, Vick got going. He had completions of 13 and 17 yards on a drive that was finished off by McCoy's nifty 11-yard TD run. McCoy broke a tackle, cut outside and ran into the end zone to get the Eagles within 14-10.
Miami Heat star LeBron James was on the field before the game. He was in town to play in an exhibition basketball game with other NBA All-Stars at The Palestra. ... The Giants were again without Pro Bowl DE Osi Umenyiora and first-round draft pick Prince Amukamara. ... The Eagles didn't have defensive ends Darryl Tapp and Juqua Parker. ... The Eagles reshuffled all three of their starting linebackers this week, moving each one into a new spot. ... Vick lined up at receiver for one play with Ronnie Brown in the shotgun formation behind center. McCoy took the direct snap and ran 3 yards.