Wyoming vs Colorado Pick & Prediction – 9/20/2025

The Wyoming Cowboys and Colorado Buffaloes will do battle in college football on Saturday night in Boulder. The Buffs are 1-2 to start the season and are desperate for a non-conference win this week. Wyoming is 2-1 to begin this year and will look for its most impressive win of the season to date. Here, I break down this contest and give you my Wyoming vs Colorado prediction.

Our Wyoming vs Colorado Pick

• Pick: Colorado -12.5
• Confidence: 3/5
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Game Snapshot

• Matchup: Wyoming Cowboys vs Colorado Buffaloes
• Date & Time: Saturday, September 20, 2025, 10:15 PM ET
• Venue: Folsom Field, Boulder, CO
• Broadcast: ESPN

Key Storylines

• Quarterback Uncertainty in Boulder: Colorado’s quarterback situation remains fluid. Senior Kaidon Salter is set to start against Wyoming after a brief benching. He has completed 68.2% of his passes for 261 yards and one touchdown. It will be interesting to see how he responds to being benched by head coach Deion Sanders.
• Wyoming’s Defensive Strength: The Cowboys boast a formidable defense, allowing just 12.7 points per game, ranking 26th in the nation. However, they face a significant test against Colorado’s offense after Wyoming’s defense has built up its stats against bad teams like Akron and Northern Iowa of the FCS.
• Colorado’s Struggles: The Buffaloes are 1-2, with losses to Georgia Tech and Houston. Their offense has been inconsistent, averaging 23.7 points per game, which ranks 95th in the FBS. They will need to improve to win this game outright, let alone cover the spread.

Quarterback Play

Colorado’s Kaidon Salter returns as the starting quarterback after a brief period of uncertainty. His dual-threat capabilities will be vital for the Buffaloes to establish an offensive rhythm. Wyoming’s defense will need to contain him to keep the game competitive.

Wyoming’s Kaden Anderson has struggled to find consistency so far this season. He has three touchdown passes and two interceptions so far and will look to bring his team an upset win here.

Betting Trends & H2H

• Wyoming: 2-1 against the spread this season.
• Colorado: 1-2 against the spread this season.
• Over/Under: Colorado games have hit the over once this season. All three of Wyoming’s games have gone under their totals.
• Head-to-Head: This is the first meeting between these teams since 2009. Colorado is 24-2-1 all-time against Wyoming.

Wyoming vs Colorado Model Projection

Score Projection: Wyoming 17 – Colorado 31

Win Probability: Wyoming 25%, Colorado 75%

Final Thoughts

The Colorado Buffaloes enter this game as 13.5-point favorites against the Wyoming Cowboys. While Wyoming’s defense has been impressive, Colorado’s offense is expected to find success at home. The Buffaloes’ need to rebound from recent losses adds motivation, making them likely to cover the spread in this matchup against a Wyoming team that will regress on defense against a power conference opponent.

Jay Sanin

Jay Sanin is a sports bettor, writer and broadcaster from New York. He is an avid New York Knicks fan and is no longer ashamed to admit it. He is also an avid New York Giants fan, and is very ashamed to admit it. His top sports to handicap are the NBA, WNBA and men’s tennis for some reason. He has watched more UAlbany Great Danes basketball than anyone should consume.

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• Source: https://ats.io/college-football/wyoming-cowboys-vs-colorado-buffaloes-pick-prediction-9-20-2025/467755/