Matt Barkley threw for 224 yards and three 17 victory over the Notre Dame conference matchup at Notre Dame Stadium.
Barkley completed 24-of-25 under center in the win for USC (6-1), which has won three consecutive contests. Curtis McNeal ran for 118 yards on 24 carries, while Robert Woods hauled in 12 receptions for 119 yards and a pair of touchdowns as well.
Tommy Rees threw for 190 yards on 23-of-37 passing to lead Notre Dame (4-3) in the loss, but the signal-caller had no touchdowns and one interception. It was a tough day offensively for the Irish, as the squad managed just 267 total yards.
The Trojans took a 7-0 lead midway through the opening period of play following a two-yard toss from Barkley to Randall Telfer.
Barkley gave the Trojans a 14-0 advantage late in the frame with a three-yard scoring strike to Robert Woods.
A 25-yard Andre Heidari field goal late in the second stanza gave USC a 17-0 edge, but Notre Dame's George Atkinson III returned the ensuing kickoff 96 yards for a score to pull the Irish within 10.
The Irish added a 25-yard David Ruffer field goal with under a minute remaining in the half to head into the break down 17-10.
An 80-yard fumble return for a touchdown by Jawanza Starling late in the third period gave the Trojans a 24-10 lead.
A 25-yard Jonas Gray scamper early in the final period of play pulled the Irish to within 24-17.
But the Trojans made it a 31-17 game midway through the frame following a 14- yard completion from Barkley to Robert Woods.
USC has prevailed in nine of the last 10 meetings with Notre Dame.