Quarterback Matt Barkley completed 23 of 30 passes for 303 yards and three touchdowns for the Trojans, including an 83-yard strike to Marquis Lee early in the fourth quarter to help absolve kicker Andre Heidari, who missed two field goals in the third and fourth quarters to keep the Utes in the game.
Lee finished with 12 catches for 192 yards and a touchdown.
The touchdown made it 31-21, and the Trojans sealed their victory just moments later when cornerback Nickell Robey intercepted Utah quarterback Jon Hays and returned it 38 yards for a touchdown and a 38-21 lead with 9 minutes, 30 seconds remaining.
The loss dropped the Utes to 2-3 overall and 0-2 in the Pac-12, and ruined a dream start.
The Trojans lost the ball deep in their own territory, leading to Utah touchdowns twice in the first four minutes.
On the second play from scrimmage, the USC snap went between Barkley's legs. When Barkley chased it down, Utah's Nate Fakahafua tore the ball from his hands and raced 8 yards for a touchdown.
Just two minutes later, Utah's Star Lotulelei recovered another fumbled snap that allowed Hays to hit Kenneth Scott for an 11-yard touchdown pass and a 14-0 lead for the Utes.
But the Trojans took over after that to snap a streak of eight straight Thursday-night victories for the Utes. USC improved to 4-1 overall and 2-1 in the Pac-12.