McKinley Wright scored 20 points, including two key drives in the closing minutes, and added eight rebounds to lead Colorado to a 69-65 victory Saturday night over USC.
Colorado (14-9, 5-6 Pac-12) won its third consecutive game, while USC (13-11, 6-5) dropped its second straight and third in its last four games.
Forward Bennie Boatwright led the Trojans with 24 points. Shaqquan Aaron added 13 points and was the only other Trojan to finish in double-figures.
The game was tied at 65-all with 1:49 to play, but the Trojans never scored again. Down by two with 19.4 seconds to play and coming out of a timeout, Derryck Thornton missed an open 3-pointer.
Colorado shot 64 percent in the second half to hold off the Trojans.
Evan Battey scored 14 points off the bench for the Buffaloes. D'Shawn Schwartz added 13 points and Lucas Siewert 12. Schwartz scored seven of Colorado's final 11 points.
It was the first time this season USC lost consecutive games at home.
Neither team could pull away in the first half, appropriately ending in a 29-29 tie. USC's biggest lead was five, Colorado's three.
The Buffaloes managed only three assists in the opening half, but outrebounded the Trojans 21-17 led by guard Wright's six boards.
Colorado: Despite winning both games in Los Angeles over the weekend, the Buffs' conference outcome was sealed when they opened Pac-12 play at 2-6. Their only hope of a NCAA bid remains the conference tournament.
USC: The loss dropped the Trojans into fifth place in the Pac-12.
Colorado returns home Wednesday to meet Arizona State, which beat the Buffaloes 83-61 last month in Tempe.
The Trojans next play Wednesday at Stanford. USC won the first meeting at home, 77-66.