Andre Roberson capped a 10-point, 13-rebound effort with a go-ahead layup late in regulation, as Colorado snapped No. 19 Oregon's 20-game home win streak with a 48-47 triumph at Matthew Knight Arena.
Oregon led the entire game until Roberson's layup with 23 seconds left gave the Buffaloes a one-point edge.
The Ducks had a chance at the other end, but E.J. Singler's fadeaway jumper with two seconds left was blocked by Spencer Dinwiddie, allowing the Buffaloes to escape with their first win in Oregon since Dec. 5, 1955.
"The final play was designed for me to get a drive, but they played really good defense and blocked," Singler said. "After that I just tried to get a good shot."
Dinwiddie finished with eight points and four assists for Colorado (15-7, 5-5 Pac-12), which has won four of its last five games.
"I'm really proud of our players, to win when you don't play your best," Colorado coach Tad Boyle said. "You have to do it at some point of the year, you just do, and multiple times sometimes because it's not always going to be pretty."
Singler and Carlos Emory each netted 14 points to lead the Ducks (18-5, 7-3), who have lost three straight on the heels of a nine-game winning streak.
Oregon carried a 28-23 edge into the second half before Dinwiddie recorded his first points of the contest with a three-point play to bring the Buffaloes within two.
The teams exchanged buckets from there until Damyean Dotson's trey sparked a 9-4 Oregon push to give the Ducks a 41-35 edge with just under 9 1/2 minutes remaining.
Oregon's lead was seven, 47-40, after Emory's dunk with 4:26 to play, but the Ducks failed to score the rest of the way, as the Buffaloes closed the contest on an 8-0 surge to earn the rare win in Eugene.
"We did not execute when it comes down to it," Oregon center Tony Woods said. "We were turning over the ball too much in the last few minutes and they were getting those second chance points."