Persa suffered the injury after throwing the game-winning touchdown pass to Demetrius Fields with 1:22 remaining. The junior completed 32 of 43 passes for 318 yards with two touchdowns and an interception.
"He'll be back and ready to for his senior year," coach Pat Fitzgerald said. "When you look at the first chapter for him as a full-time starter, it's pretty impressive. One thing I know about Dan is he won't be satisfied, No. 1. No. 2, you better look out because he's going to come back."
His 20-yard TD to Fields capped Northwestern's winning drive. But while the Wildcats were celebrating, Persa was on the ground clutching his right leg.
He wasn't hit on the play, Fitzgerald says Persa heard a pop.
Redshirt freshman Evan Watkins is expected to take over at quarterback for the rest of the season.
Adam Rittenberg covers Big Ten football for ESPN.com. He can be reached at firstname.lastname@example.org. Information from The Associated Press was used in this report.