For the first time since 2009, Wyoming is set to take on neighboring rival Colorado. Both schools come into Saturday’s matchup with something to prove. After losing two of their first three games, Deion Sanders’ Buffaloes need a win desperately. For the Cowboys, a victory here would match last season’s dismal 3-9 campaign. Which of these squads will come out on top tonight? Below is my prediction and pick for College Football Week 4’s game between the Wyoming Cowboys and the Colorado Buffaloes.
Colorado enters this contest as 13.5-point favorites (-112) over Wyoming, with the over/under set at 44.5 points on DraftKings Sportsbook.
Colorado vs. Wyoming prediction, preview
Let’s start with the Buffaloes, who have looked shaky without the leadership of Travis Hunter and Shedeur Sanders. The biggest issue for the team has been under center, where CU has already cycled through two different passers. Kaidon Salter entered the year as the starter, but poor showings vs. Georgia Tech and Delaware lost him the job. Backup Ryan Staub was just as bad against Houston in Week 3, handing Salter yet another opportunity tonight.
At this point, it’s difficult to make any sense of this Colorado passing game. The Buffs haven’t been much better on the ground, averaging 124.3 rushing yards per game. That’s the second-lowest mark in the entire Big 12. On defense, the team has surrendered a conference-worst 430.0 yards to their opponents. To be fair, games against Georgia Tech and Houston aren’t exactly walks in the park. Still, for a school that came close to a playoff berth last year, it’s an incredibly disappointing start.
Wyoming does represent a step down in terms of competition for the Buffaloes. Regardless, this group should not be overlooked. Head coach Jay Sawvel has built his roster with a strong emphasis on defense. The Cowboys have allowed just 12.7 points per game to opponents, 27th-best in college football. However, the team was throttled 31-6 last week vs. Utah. Quarterback Kaden Anderson has thrown for just 535 yards with a mediocre 58.5% completion percentage. If Wyoming is going to find success on offense, it’ll likely come via the run game. Three different Cowboys players have recorded at least 130 rushing yards thus far. They’re led by running back Sam Scott; the senior has gained 203 yards and three touchdowns.
Wyoming vs. Colorado pick, best bet
On paper, Colorado is clearly the more talented team in this matchup. Still, this program has looked absolutely brutal for most of 2025. In comparison, the Cowboys have been able to beat up on less-than stellar opponents. However, a dominant run game means controlling time of possession. By limiting the amount of touches for Salter and CU, Wyoming should manage to keep things close. The visitors are poised for an impressive showing in Boulder on Saturday.
