Jenkins left Saturday's game in the first half after a teammate stepped on his left foot. Trainers worked with Jenkins on the sideline, and he was able to walk to the locker room under his own power.
"After receiving information late in the afternoon following an MRI and a weight-bearing X-ray and also awaiting to talk to Brandon Jenkins and his mother, it was determined that Brandon will miss the 2012 season with a Lisfranc injury," Seminoles coach Jimbo Fisher said in a statement released by the school.
CBS Sports earlier reported Jenkins' situation.
Jenkins was a preseason All-ACC selection and on the watch lists for the Bednarik, Camp and Nagurski awards after leading the Seminoles in sacks each of the past two seasons. He nearly left FSU after the 2011 season to enter the NFL draft, where he was widely projected as a potential first-round pick.
Jenkins recorded his first sack of the season in the first quarter against Murray State, moving him to within 2½ sacks of third place all-time in school history.
With Jenkins out, the Seminoles will turn to Cornellius "Tank" Carradine.
"Tank, you guys don't know him yet. You'll be surprised. He'll be sitting here at the end of the season and you won't want to talk to us anymore," fellow defensive end Bjoern Werner said.
Following Saturday's game, a 69-3 romp, Fisher said he saw his corps of defensive ends as a strength of the team.
"Tank's not really a third defensive end. They're 1A, 1B and 1C," the coach said.