Week 3 College Football Predictions: NCAAF Best Bets for Friday, September 12

Sep 6, 2025; Houston, Texas, USA; Houston Cougars running back Dean Connors (44) runs with the ball as Rice Owls linebacker Andrew Awe (0) attempts to make a tackle during the first quarter at Rice Stadium.
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Sam Avellone

CFB

Long-time suffering Browns fan born and raised in the greater Cleveland, Ohio area who now resides in SEC country. University of South Carolina alum. Sports handicapper for close to 10 years with a primary focus on NCAAB while enjoying NFL, PGA, NCAAF, NBA, and Soccer. For Sam Avellone media enquiries, please email contact@pickswise.com.
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We are full-steam ahead on this college football season, as the Week 3 slate presents multiple big-time matchups bearing seasonlong significance to conference title races and postseason eligibility. Before we get to the meat and potatoes of the college football card, Friday provides us with an appetizer of 3 FBS vs FBS matchups with varying storylines.

Who is playing quarterback for Colorado? Can Kansas State fix its season in its first true road game? What’s going on with Nico Iamaleava and the Bruins?

After browsing through the matchups, I’m targeting one angle on Friday’s limited card. Here is my best bet for Friday, and don’t forget to find the rest of our college football best bets for Week 3’s massive slate.

CFB Friday best bet: Houston Cougars 1H -2.5 (-115)

Odds available at BetMGM at the time of publishing.

News broke earlier this week that third-string quarterback Ryan Staub is getting the start on Friday night in Colorado’s first true road game of the season. It’s a puzzling decision considering Coach Prime brought in Kaidon Salter from Liberty and a four-star freshman in Julian Lewis in the offseason. Even more bizarre was Prime refuting the reports on Wednesday, saying Staub was simply playing well and taking a majority of the first-team reps in practice. He also said a decision for Friday’s game had yet to be made.

If you can draw anything certain from that, well that makes one of us. Although, any sort of quarterback drama isn’t exactly ideal, especially when you’re hitting the road for the first time against a strong defense led by a well-regarded coach in Willie Fritz. This Colorado offense has struggled to put itself into scoring situations (101st in total non-garbage time opportunities through Week 2), and with the quarterback drama, I don’t have much faith in the Buffaloes waking up offensively on the road, under the lights in a primetime game against a defense that was top 50 in scoring, scoring opportunities allowed, points per opportunity, and total defense in 2024.

I’m expecting Houston’s offense to have chemistry and fluidity to it early against a Colorado defense that was extremely poor against Georgia Tech’s rushing attack and has surrendered 7 explosive passes through 2 weeks despite its most recent game being against Delaware. I give the edge to the Cougars not only on both sides of the ball in this matchup, but on the sidelines from a coaching and preparation standpoint with Fritz. Take Houston to cover the first half against Colorado at anything -4 or better.

Find our full Colorado vs Houston prediction for this Big 12 battle on Friday night

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