Coach Lane Kiffin announced Sunday that Max Wittek will make his first career start in place of Barkley.
Barkley was injured in the final minutes of the Trojans' 38-28 loss to UCLA when he was sacked by Anthony Barr. Barkley stayed down on the field for a long moment, and didn't play on USC's final series.
Barkley was a strong Heisman Trophy candidate last season and again this summer after electing to return for his senior year.
But his season has been inconsistent along with his team. Barkley has passed for 3,273 yards and 36 touchdowns, but has thrown a career-worst 15 interceptions.