Houston Cougars vs Colorado Buffaloes Picks and Predictions September 12th 2025

Colorado vs Houston Picks and Predictions — September 12, 2025

The Colorado Buffaloes head south to take on the Houston Cougars in the Big 12 opener for both programs on Friday, September 12, 2025. Deion Sanders has kept his quarterback decision under wraps, while Houston enters riding an undefeated start.

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Opening Odds: Houston -6.5, Colorado +6.5, Total 49.5

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The Colorado Buffaloes Can Win If…

Colorado’s offensive spark will depend on quarterback Ryan Staub — if he gets the nod. Against Delaware, Staub threw for 157 yards and two touchdowns on just 10 attempts, pushing the Buffaloes’ passing game into rhythm.

The Buffaloes must protect the football and avoid stalling drives. Their defense has held opponents in check but faces a much stronger rushing attack in Houston. Colorado’s ability to stretch the field with explosive plays is their best path to an upset.

The Houston Cougars Can Win If…

Houston dominated Rice last week with a balanced attack. Running back Dean Connors ripped off 132 rushing yards and two scores, while quarterback Conner Weigman added both a passing and rushing touchdown.

Houston’s defense ranks No. 4 nationally, and coordinator Willie Fritz will have his unit ready regardless of which Colorado QB takes snaps. If Houston controls time of possession on the ground while forcing Colorado into obvious passing situations, the Cougars should cover comfortably at home.

Key Betting Trends

The Lean

Model Projection: Houston 28, Colorado 17
Pick: Houston -6.5
Total Lean: Under 49.5

Houston’s defensive dominance and strong rushing attack give them the edge. Colorado’s QB uncertainty adds volatility, but unless Staub delivers another big performance, the Cougars should remain unbeaten.

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