Miami coach Al Golden confirmed the extent of the injury on Sunday.
Johnson flew home with his teammates early Sunday morning and will have surgery in the coming days, a source told the Associated Press.
Quarterback Stephen Morris said Johnson was in good spirits after the game.
"He's doing fine," Morris said. "He's in great spirits right now, talking to his teammates, trying to encourage us and everything. Duke is Duke, and he'll be OK."
Johnson was injured on a fourth-down play late in the third quarter, when his right leg twisted awkwardly beneath him at the bottom of a pile. He was helped off the field and could not put any weight on his right ankle.
He was in tears on the sideline after he was injured, and was later carted to the locker room.
Reporters saw Johnson leaving the stadium with his leg in a cast.
Johnson has developed into a workhorse back for the Hurricanes this season. The No. 2 rusher in the ACC finished with 23 carries for 97 yards against the Seminoles and is the best player on the Miami offense.
With Johnson out, Miami figures to use running back Dallas Crawford in the feature back role going forward. Crawford wrote about his new role on Twitter early Sunday:
There's a lesson in every loss.. Learn from it.. and move on
— dallas crawford (@GoLive_25) November 3, 2013
Information from The Associated Press was used in this report.