"It's time for me to go," said Powe, who will bypass a chance for an extra season of eligibility for the Rebels (4-8).
Powe will turn 24 in March and explained that "the NFL doesn't draft 25-year-olds in the first round." He said he made his decision on Friday. He plans on remaining in school and hopes to graduate later this year from Ole Miss.
Powe amassed 27 tackles and three sacks this season for the Rebels.
Bruce Feldman is a senior writer at ESPN The Magazine.