Colorado athletic director Rick George said he would name an interim head coach ahead of the team's final game of the season. With a win, Colorado would be bowl-eligible.
"I want to thank Mike for six seasons of hard work and dedication to the program, both on and off the field," George said in a statement. "There's no doubt that the 2016 season was magical, and it appeared we were headed back to taking our place among the nation's elite. However, analyzing the direction of the program over the last two years, I felt this is the necessary time to make a change."
MacIntyre was the 2016 national coach of the year after leading Colorado to the Pac-12 title game, though the Buffaloes have gone 10-13 since and have lost six straight games this season.
In stints with San Jose State (2010 to 2012) and Colorado (2013 to 2018), MacIntyre has gone 46-65 and reached one bowl game with Colorado in 2016 (an Alamo Bowl loss).
Last season had its promise, as the team was 5-4 and a single victory away from being blow-eligible. Instead, the Buffaloes lost three straight to close the year.
This season, the Buffs started 5-0 and were ranked No. 19 before their current losing streak hit. After Colorado's 30-7 loss to Utah on Saturday, MacIntyre appeared to see the writing on the wall.
"The thing about this business that's tough is, when you do good, everybody's asking why you're leaving," he said during his press conference, per Mark Kiszla of the Denver Post. "They get mad at you when you're leaving. I could've left (for) three good places, and stayed. That's just the way it is. When you're losing, they want to get rid of you. You can never win as a head coach on that, and I understand that."