The running back tore his anterior cruciate ligament Saturday during the 9-1 Cardinals' 45-26 loss to Syracuse.
"He didn't take the news very well. He was having a great season, so he was disappointed," Louisville Coach Charlie Strong said Monday.
Jeremy Wright is expected to pick up the slack with Perry out. Wright has 680 rushing yards and nine touchdowns, plus 193 receiving yards on 24 catches.
"I think we'll be OK in the running game," Strong said. "Senorise was a big part of our offense, but Jeremy Wright will take more of the load."
Louisville has the week off before going against Connecticut Nov. 24.