Boulder, CO – Matt Barkley set a school record with six 17.
Barkley threw for 326 yards on 26-of-40 passes for the Trojans (7-2, 4-2 Pac-12), who were less than a week removed from falling to Stanford in triple overtime.
Robert Woods and Marqise Lee were once again Barkley's top targets, combining for 261 yards and four touchdowns on 19 catches.
The Buffaloes (1-9, 0-6) have yet to record a Pac-12 victory.
Colorado's Tyler Hansen passed for 249 yards and two touchdowns, including a 37-yard strike to Toney Clemons on the game's opening possession.
The lead was short-lived, however, as the Trojans scored 28 straight points to take control.