Coach Greg Schiano told reporters on Tuesday that James will miss the remainder of the season due to the injury.
James, filling in as the starter for Doug Martin, was carted off the field with a left ankle injury early on the opening drive of the game.
James was rolling on the ground in pain after another player fell onto his foot, causing the ankle to be twisted awkwardly. NFL Media Insider Ian Rapoport reported that the X-rays taken Monday night revealed the fractured ankle, which Schiano confirmed after the game.
General manager Mark Dominik heaped praise on James in a pregame conversation with NFL Media's Jeff Darlington.