Jacobs initially suffered a soft-tissue injury against South Dakota State in Week 1, missed the next two games before returning against Rutgers last week, only to have the injury get worse after playing limited snaps in Saturday's game.
Ferentz has not specified where the injury is located.
"Unfortunately, we did get bad news on Jestin," Ferentz said. "It didn't sound good the other night and it's been confirmed. So he's going to have to have surgery and is going to miss the rest of the season.
"That's obviously a very tough break. Tough on the team but, more importantly, just tough on the individual. And that's the worst part about injuries."
Jacobs had 53 tackles last season.
"It's just disappointing," Ferentz said. "It just stinks. ... That's the thing about injuries. I'm not sure everybody understands -- if you're a college football player, it's important to you to play those 12 games. That's all you have guaranteed and he just lost whatever we got left."