Brees threw two touchdown passes to take his streak to 51 as the Saints inflicted a fourth straight defeat on the Eagles.
With the Eagles in the shadow of the end zone, Saints defender Patrick Robinson picked off a pass by Philadelphia's Michael Vick and returned the ball 99 yards for a touchdown as the Saints took a 7-0 lead after the first quarter.
There was talk a struggling Vick could be benched for the game while head coach Andy Reid is fighting for his job.
Sensing blood, the Saints went for the jugular, attacking Vick with seven sacks and several other big hits to inflict a fourth successive defeat on the visiting Eagles.
Alex Henery kicked a 22-yard field goal early in the second quarter to put the Eagles on the scoreboard but the Saints answered on a 22-yard touchdown run by Chris Ivory to seize a 14-3 lead.
Brees flipped a 1-yard touchdown pass to Marques Colston with 73 seconds to play in the second quarter, giving the Saints a 21-3 half-time edge.
Vick connected with DeSean Jackson on a 77-yard touchdown pass early in the third quarter and Henery added a 37-yard field goal to pull the Eagles within 21-13.
But the Saints answered when Brees tossed a 6-yard touchdown pass to Jimmy Graham late in the third quarter to create the final margin.
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