Cameron Marshall rushed for 141 yards and three game losing streak to Southern 22 victory over the 23rd-ranked Trojans.
Brock Osweiler tossed for 223 yards and two touchdowns on 25-of-32 passes for the Sun Devils (3-1, 1-0 Pac-12), who had four takeaways and did not turn the ball over.
Matt Barkley was 21-of-33 for 227 yards and one TD pass for USC (3-1, 0-1), but was intercepted twice, including one returned 41 yards by Shelly Lyons to cap 22 unanswered points by ASU.
The Trojans trailed 21-9 after settling for three Andre Heidari field goals in the first half.
Barkley started putting things together after the break, completing all five of his passes on the opening touch, including a 24-yard scoring strike to Marqise Lee.
Marc Tyler ran in for a 10-yard score to give USC its first lead, 22-21, with 6:41 to go in the third, but the two-point conversion failed and it was all downhill for the visitors from there.
The Sun Devils answered immediately with an eight-play, 76-yard march that Marshall capped with a three-yard run.
Marshall tacked on a four-yard TD run midway through the fourth to end another lengthy drive, and Lyons put the finishing touches on the victory by hauling in Barkley's rushed throw and returning it 41 yards for a score.
Marshall gave a sign of things to come with a 70-yard touchdown scamper on the fourth play from scrimmage, and Osweiler threw short TD passes to Gerell Robinson and Jamal Miles in the second.
Heidari hit field goals of 41, 29 and 23...Tyler finished with 149 yards on 22 carries, while Robert Woods caught eight passes for 131 yards.