It will be Vick's first NFL start since Dec. 31, 2006, when he was a member of the Atlanta Falcons.
Vick will replace quarterback Kevin Kolb, who coach Andy Reid ruled out Friday.
Vick came in for Kolb in Week 1 when the Eagles' starting quarterback was knocked out of the game with a concussion. Kolb remained out of practice Friday.
Reid had said Kolb was "making progress" from the concussion but hadn't passed the next phase of his concussion testing.
The NFL has strict return-to-play guidelines for players who show concussion symptoms. Kolb won't be allowed to practice or attend meetings until he passes the next test.
Vick nearly rallied the Eagles to a comeback victory over the Green Bay Packers, completed 16 of 24 passes for 175 yards and one touchdown, and scrambled for 103 yards.
"I had the old feel back," Vick said Sunday.
"I still feel like I can play at a high level," Vick said. "I feel like if I had been out there for four quarters, maybe we would have had a chance to win the game. I feel like I'm like 25 or 26 again, even though that's not the case."
Vick missed the 2007 and 2008 seasons while serving an 18-month sentence in federal prison for his role in a dogfighting operation. Vick signed a two-year contract with the Eagles last summer, and saw limited action mostly in a variation of the Wildcat formation.
Eagles linebacker Stewart Bradley was also ruled out against the Lions because of a concussion.
Information from ESPN.com's John Clayton and The Associated Press was used in this report.