Wyoming Cowboys vs Colorado Buffaloes Prediction, Odds and Picks for Today, 09/20/25

The Wyoming Cowboys head south from Laramie to Boulder to battle the Colorado Buffaloes in a border-war game. Wyoming has had trouble scoring points all season, including a 31-6 loss against Utah last weekend. It picked up a 10-0 win in Akron on Aug. 28, and it barely won 31-7 against FCS Northern Iowa at home on Sept. 6. That’s three games, and that’s three under results for the Cowboys. Oddly enough, all of those games had a line of 47.5, so this marks the lowest of the season.

The Buffaloes have managed 20 points in each of their games against FBS opponents, with a 31-7 win over FCS Delaware on Sept. 6. There are plenty of parallels between Colorado and Wyoming, but the Buffaloes have the flashier coach and higher-caliber recruits — though these teams aren’t as far apart as most think. Wyoming has a solid defense, but it fails to score points. Colorado’s defense is so-so, and its offense is a tick better than Wyoming. However, the Buffs will have difficulty moving the ball against the Cowboys D. Look for this game to be a 30-10 kind of a game. While 44.5 is a low number in this day and age of college football, it’s worth a play here.

Wyoming vs Colorado prediction: Under 44.5 (-110) at time of publishing. Playable to 43.5.

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