Vick, substituting for the injured Kevin Kolb, went 21-of-34 for 284 yards and ran the ball seven times for 37 yards for Philadelphia (1-1).
Kolb was held out of the game after suffering a concussion the Eagles' loss to Green Bay last week.
Lions quarterback Shaun Hill, making his first start for the team, went 25-of-45 through the air, gaining 335 yards and connecting on a pair of touchdown passes.
Rookie running back Jahvid Best racked up 232 yards and scored three times for Detroit (0-2).
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