Matt Barkley threw two touchdown passes and Southern California took advantage of five turnovers from California to win its eighth straight game in the series, 30-9 on Thursday night.
Marqise Lee and Brandon Carswell caught TD passes but it was the defense that bailed out USC (5-1, 3-1 Pac-12) on a night its offense struggled to click.
Making matters even worse, the Trojans lost Lee to an apparent right arm injury in the first half and leading rusher Marc Tyler to a shoulder injury in the third quarter.
USC now has nine days to prepare for its matchup at Notre Dame. The Irish, 4-2, are on the bye this week. The game next Saturday will be the first night game at Notre Dame Stadium in 21 years.
After allowing 84 points and 946 yards the previous two games, the Trojans kept Cal off the scoreboard until late in the third quarter and doubled their turnovers caused this season with three interceptions and two fumble recoveries.
Zach Maynard committed four of Cal's five turnovers -- surpassing the team's season total coming into the game -- and the Bears dropped their sixth straight conference game since late last season. Cal is off to its worst conference start ever under coach Jeff Tedford.
Maynard threw for 294 yards and ran for a touchdown and his half-brother, Keenan Allen, had a career-high 13 catches for 160 yards but it wasn't enough to overcome the litany of mistakes.
This series has been decidedly one-sided ever since Cal upset USC 34-31 in triple overtime back in 2003. The Trojans have won eight straight and it hasn't even been close of late with USC outscoring Cal 125-29 the last four years.
Cal fell behind 23-0 early in the third quarter before the offense finally got going, with Maynard leading the Bears to a field goal and then scoring on a 3-yard with 6 seconds left in the third to cut it to 23-9.
But Maynard's third interception midway through the fourth quarter led to Curtis McNeal's 2-yard touchdown run that made it 30-9 with 5:14 remaining.
The Bears turned the ball over four times in the first half, including three alone by Maynard, and failed to convert a fake punt as they fell behind 20-0 at the break.
It wasn't quite as bad for the Bears as the game a year ago in Los Angeles when USC led 42-0 at the half. Cal's defense actually did a decent job defending Barkley and the Trojans' high-powered offense but USC took advantage of short fields for its scores.
Allen fumbled on Cal's fourth play from scrimmage to set the tone for the game, but the Bears survived that miscue thanks to an odd play call by USC coach Lane Kiffin.
On fourth-and-goal from the 8, the Trojans lined up in an off formation and snapped the ball diagonally to Rhett Ellison, who dropped it for a turnover.
The Trojans capitalized on the next turnover as Nick Perry forced a fumble by Maynard that led to Andre Heidari's first field goal.
USC then broke the game open with 17 points in the second quarter, getting a 39-yard TD catch from Lee over fellow freshman Stefan McClure, a field goal after Chris Galippo intercepted Maynard's pass deep in Cal territory and a 7-yard TD pass from Barkley to Carswell after punter Bryan Anger was stopped on a fake that made it 20-0.
Barkley completed 19 of 35 passes for a season-low 195 yards. Robert Woods, the nation's top receiver, was held to five catches for 36 yards.
Cal's only sustained drive of the half ended in the final minute when Maynard threw into triple coverage and was intercepted in the end zone by Dion Bailey.