LaMichael James ran for 219 yards and three touchdowns.
The win puts the Ducks up for a likely berth in the Rose Bowl.
Rick Neuheisel tipped his hat to the UCLA fans in his last game as coach. The former Bruins quarterback was fired this week after four seasons with his alma mater.
While the Bruins (6-7) played with passion for their outgoing coach and kept it closer than many thought they would, it was not enough to overcome the Ducks (11-2), who head to a BCS bowl for the third straight season.
Darron Thomas threw for 219 yards and three touchdowns, becoming Oregon's career leader with 63 TD passes.
The Associated Press contributed to this report.