The offense turned the ball over late and the defense couldn't get a stop in the final minutes.
With the game on the line, No. 19 Oregon wilted as Colorado rallied to upset the Ducks 48-47, despite not leading until the final basket.
Andre Roberson scored off his own miss with 29 seconds left and Colorado recorded the final eight points of the game.
"Disappointing," Oregon coach Dana Altman said with a shake of his head.
Carlos Emory and E.J. Singler scored 14 points to lead the Ducks (18-5, 7-3 Pac-12), whose third consecutive loss snapped a 20-game home winning streak.
Singler had a chance to win it for Oregon but his long jumper was tipped by Spencer Dinwiddie and fell into Roberson's hands under the basket with 1.1 seconds left.
"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."
Arsalan Kazemi also had 11 rebounds and six points for the reeling Ducks, who are 1-3 without starting point guard Dominic Artis, who missed his fourth straight game with an undisclosed foot injury.
"Dominic spreads the floor," Altman said. "The floor has shrunk and it's been hard to drive to the hoop."
Roberson finished with 10 points and 13 rebounds for the Buffaloes (15-7, 5-5), who trailed 47-40 with just under four minutes to play when they rallied for their lowest scoring victory of the season.
"We're just trying to get back on track, trying to get where we want to be," Roberson said. "This was one step forward."
"Huge win" said Colorado coach Tad Boyle, whose team was coming off a 58-56 loss to lowly Utah, the Buffaloes' only blemish in their last five games. "That was a head-scratcher. But when we're dialed in, we're pretty good."
They were certainly that against Oregon late in the game.
The Ducks led 28-23 at halftime and never trailed until Roberson's last basket on a possession that was set up by Oregon's fourth straight turnover, an offensive foul called on Singler at the other end.
Roberson took a pass from Dinwiddie under the basket but had his first attempt blocked from behind by Kazemi.
"'Go get it, go get it,'" Roberson said he told himself. "'If you want to win this game, put it all on the line.'"
He got it, and went back up for the basket.
"Andre can get it to the rim awfully quick," Boyle said.
Colorado had 17 second-chance points altogether, including two more by Roberson with 2:12 to play that made it 47-46.
Dinwiddie scored seven of the Buffaloes' first 10 points in the second half as they cut their halftime deficit to 35-33 with 14:19 to play.
Ben Carter answered for Oregon with a jumper from the baseline and Emory followed with a pair of free throws — the Ducks' first trip to the foul line in the game — to extend the lead to 39-33 with 11:02 to go.
Oregon's lead grew to 47-40 on a dunk by Emory with 4:26 to play. But those were the Ducks' final points as they went 0 for 3 from the field the rest of the way.
"I definitely sensed a little panic when we started making a little comeback," Roberson said. "You could definitely sense they were feeling pressure to score the ball."
Oregon shot just 36.2 percent from the field and had seven of its 12 turnovers in the final 7:39.
Colorado also had 12 turnovers and shot just 36.5 percent, but the Buffaloes got hot at the end of the game, going 3 for 5 from the field in the final four minutes.
"I'm more disappointed with our defense than our offense," Altman said. "We didn't get stops and gave up too many second-chance points."
The Ducks broke an early tie with a 10-2 run to take a 15-7 lead by the 10:58 mark of the first. Emory had four points during that stretch, while Colorado's only points came off a monster two-handed slam of a rebound by Roberson over Kazemi.
Kazemi got his revenge on the Ducks' ensuing possession, spinning to the basket for a one-handed dunk off a rebound. The typically subdued Kazemi then flexed his biceps as the Oregon student section erupted.
Trailing 17-11, the Buffaloes got back-to-back 3-pointers from Jeremy Adams and Askia Booker to tie the score with 5:47 to play in the half.
But Colorado cooled off, making just one of its next seven attempts from the field as the Ducks went up 26-19 with 2:19 to play on a 3-pointer by Singler, who had 12 points in the first half.