Colorado vs Houston Prediction, Pick & Odds (Friday, Sep. 12)

• Houston is a 4.5-point favorite over Colorado on Friday night
• Ryan Staub will make just his second career start, and first since 2023 for the Buffaloes
• Keep reading for my Colorado vs Houston prediction, pick and odds

The Friday night lights shine on Deion Sanders and Colorado (1-1) this week, as they visit Houston (2-0) in Big 12 action. The Cougars have thrashed each of their first two opponents, and online sportsbooks expect another victory in the college football odds.

Kickoff is scheduled for 7:30pm ET from TDECU Stadium, with ESPN providing the broadcast coverage.

Colorado vs Houston Prediction and Pick

• Houston -4.5 (-110 at Bet365)

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They say if you have two quarterbacks, you don’t really have one. But how does that apply when you have three QB’s? That’s the situation facing Coach Prime these days, as he’s given Kaidon Salter, Ryan Staub and Julian Lews playing time through two weeks.

Salter was expected to be the full-time starter, but his underwhelming start has Sanders looking for a change. Colorado will start Staub on Friday in Houston, after the third-year sophomore shined last week against Delaware.

Staub was 7-of-10, for 157 yards and 2 TD, and brings a deep ball element that Salter does not possess. Salter entered the year with a 23-6 record as a starter with Liberty, but is averaging only 5.9 yards per throw on 44 attempts. The senior is a former 1,000 yard rusher with the Flames, so Coach Prime is still expected to use Salter occasionally versus Houston to keep the defense guessing.

What’s surprising about Staub’s anointment as starter is that he began the year as the third option. Lewis was the number 12 recruit in the 2025 class and enrolled a year early for a chance to compete with the Buffaloes. Sanders wants to bring Lewis along slowly, opening the door for Staub to play. It will be just the second start of Staub’s career, and first since 2023.

He’ll have his hands full with Houston on Friday for a pair of reasons. Number one is the lack of production from the Colorado rushing attack. That unit is averaging only 3.9 yards per carry, while RB’s Simeon Price and Micah Welch have combined for only 1 TD.

The second reason is the strength of the Cougars defense. Houston is allowing only 4.5 points per game, and have limited enemy offenses to 3.3 yards per play.

Houston Cougars Defensive Stats

Granted, the Cougars’ first two games have been against Rice and SF Austin, who are far from contenders in the college football playoff odds. However, you can only beat who’s on your schedule, and so far Houston has outscored their opposition 52-9.

Which brings us to the Cougars offense. Houston has a five-star QB transfer in Connor Weigman, and a rushing attack that just piled up 204 yards on the ground versus the Owls.

Weigman has played mistake-free football so far, and the Cougars should find success both through the air and on the ground against the Buffaloes. Colorado’s pass defense is one of the weakest in the Big 12, while their run defense was bludgeoned for 320 yards by Georgia Tech in Week 1.

I’m predicting a big offensive performance from Houston on Friday. That, combined with their stingy defense, and the uncertainty of how Staub will look against top-flight conference competition, has me taking the Cougars -4.5 as my favorite Colorado vs Houston pick.

Colorado vs Houston Odds

The most favorable odds we can find on Houston -4.5 is -110 is Bet365. They’re offering Colorado at +165 to pull off the upset, while the total is listed at 45.

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Odds as of September 11 at Bet365. New customers can claim the Bet365 promo code and get a bonus to bet on Week 3 college football.

Per the college football public betting trends, sharp money is also on the Cougars. Houston is drawing 55% of the spread bets so far, but those tickets account for 77% of the money wagered.