The school said Thursday that Graham, the Big East's leading rusher, will need surgery to repair the knee. Graham was averaging 134 yards a game for the Panthers but crumpled to the ground just as he was tackled at midfield on Pitt's first possession against UConn.
The Panthers also lost junior wide receiver Cameron Sadler (fractured sternum) and freshman offensive lineman Matt Rotheram (fractured ankle) for the year after they were injured against the Huskies.
Coach Todd Graham called the injuries "heartbreaking."
Pitt (4-4, 2-1 Big East) hosts Cincinnati on Nov. 5.