Mayo played despite reports that he may have violated NCAA rules by accepting free tickets to the Denver Nuggets-Los Angeles Lakers game Monday night.
Taj Gibson added 14 points and 14 rebounds for the Trojans (12-6, 3-3 Pacific-10).
Lathan Wallace led Oregon State with 11 points, and was the only Beaver in double figures.
Fresh off the firing of coach Jay John, Oregon State (6-13, 0-7) set season lows in points, second-half points (19) and shooting percentage(27.7 percent).
Mouton took over the job Sunday night and immediately dismissed center C.J. Giles from the team. He made another statement Thursday, choosing not to start Marcel Jones -- the team's second-leading scorer and only senior. Jones came off the bench to score five points on 1-of-11 shooting.
Jefferson, coming off a career-high 25 points and nine rebounds in USC's upset win over UCLA, displayed hustle and acrobatics on both ends of the floor. He was 9-of-12 from the field with seven rebounds and three steals.
Mayo entered the game as the Pac-10's second-leading scorer at 19.7 points per game. The freshman received the NBA tickets from Nuggets star Carmelo Anthony, and told reporters this week that they had a face value of $230 each.
USC jumped to an 18-4 lead, but the Beavers went on a 15-2 run in the last 5:02 of the half and trailed 27-25 at the break.
If Oregon State had hopes of ending its eight-game losing streak, they faded early in the second half. The Trojans opened the final 20 minutes on an 11-0 run. Mayo knocked down his third 3-pointer during the run and then dished off to Jefferson for a fastbreak layup.
Jefferson's alley-oop slam at 14:41 put USC up by 15 and the Trojans coasted to their sixth straight win over the Beavers.
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