USC kept it close for much of its final home game, but Oregon pulled away for a 78-63 victory Saturday at the Galen Center.
Senior guard Pe'Shon Howard scored 20 points for the Trojans, who fell to 10-19 overall and 1-15 in the Pac-12 Conference.
Forward Mike Moser scored 20 points and Joseph Young had 16 for Oregon, which improved to 20-8 and 8-8.
USC has lost 10 consecutive games and 15 of its last 16 under first-year Coach Andy Enfield.
USC finishes the regular season with a trip to Washington State on Thursday and Washington on Saturday.
The Pac-12 tournament begins March 12 in Las Vegas.
As part of Senior Day festivities, Enfield started an all-senior lineup of Howard, guards J.T. Terrell and Daniel Munoz, forward D.J. Haley and center Omar Oraby.
Howard scored 16 points in the first half when USC built a short-lived seven-point lead, but the score was 36-36 at halftime.
The Trojans stayed close through much of the second half, tying the score, 58-58, on a basket by Byron Wesley before Oregon began to pull away.
Elgin Cook's basket and free throw started the Ducks on the their way.