Manning threw two touchdowns in three series before departing Thursday night and Indianapolis held on for a 23-15 victory over Philadelphia.
The Colts looked a lot better than they did in last week's loss against Minnesota. Manning took Indy 81 yards on the opening series, closing it with a 3-yard TD pass to Anthony Gonzalez.
The three-time league MVP finished 10 of 14 for 167 yards with two touchdowns in less than 11 minutes. His backup, Curtis Painter was 11 of 19 for 116 yards with one interception but led the Colts to three field goals.
Defensively, the Colts were better, too. They forced two three-and-outs on the first four series and responded to Manning's lone miscue - a fumble deep in his own end - by forcing another turnover when Dwight Freeney swatted the ball away from Donovan McNabb. Indy's Keyunta Dawson recovered.
Manning took advantage right away, finding Reggie Wayne down the left sideline. Wayne scooted down the sideline, then made a nifty inside cut near the 10-yard line to avoid a defender for a 76-yard TD to give Indy a 14-0 lead.
That was good enough to get the Colts' starters out of the game.
But the Eagles were playing without four of their five projected offensive line starters. Starting running back Brian Westbrook did not make the trip, starting fullback Leonard Weaver left in the first quarter with a knee injury and Vick was not eligible to play.
Three Eagles defensive starters also missed the game.
At times, Philadelphia coach Andy Reid looked exasperated with the mistakes.
They had six penalties accepted in each half. They squandered a scoring chance at the end of the first half by mismanaging the clock and failed to convert a fourth-and-1 in the third quarter.
Philly's first score came when DeSean Jackson split two defenders down the middle of the field and McNabb threw a perfect 39-yard strike for the TD to make it 14-7. Jackson celebrated by taking a bow late in the first quarter.
Philadelphia didn't score again until Adam DiMichele found Brandon Gibson for a 21-yard TD with 26 seconds to go.
NOTES: Manning was presented with his third MVP trophy at halftime. ... The Colts played without six starters, including Bob Sanders and Adam Vinatieri, who have not yet practiced. ... McNabb was 5 of 7 for 77 yards with one touchdown. ... There were no protests outside the stadium regarding Vick, though a few fans brought in signs to express concerns about last week's signing. ... The Colts lost three players with injuries during the game. Safety Matt Giordano left with a groin injury, running back Mike Hart hurt his ankle and Chad Simpson departed with a left shoulder injury.