Colorado vs. Houston Prediction, Odds and Key Players to Watch for College Football Week 3

Houston is favored at home in Week 3.

Houston Cougars quarterback Conner Weigman is looking to lead his team to a 3-0 start. / Troy Taormina-Imagn Images

Deion Sanders and the Colorado Buffaloes picked up their first win of the 2025 season in Week 2, beating Delaware 31-7 behind a strong showing from third-string quarterback Ryan Staub.

That’s right, Sanders ended up rolling with Staub, who threw a pair of scores on Saturday, after both Kaidon Salter and Julian Lewis struggled a bit. Salter entered the season as the starter, but he’s thrown just one score in two games.

On Friday night, the Buffaloes are on the road against the Houston Cougars, who are 2-0 this season after dominant wins over Stephen F. Austin and Rice. Houston has allowed just nine points all season long, and running back Dean Connors is averaging 6.5 yards per carry while rushing for over 90 yards per night. 

Oddsmakers have set the Cougars as favorites at home in this matchup, but can they cover against a Colorado team that may be starting a new quarterback? 

Here’s a breakdown of the odds, players to watch and my prediction for this Week 3 clash. 

Colorado vs. Houston Odds, Spread and Total

Odds via DraftKings Sportsbook

Spread

• Colorado +4.5 (-112)
• Houston -4.5 (-108)

Moneyline

• Colorado: +170
• Houston: -205

Total

• 43.5 (Over -115/Under -105)

Colorado vs. Houston How to Watch

• Date: Friday, Sept. 12
• Time: 7:30 p.m. EST
• Venue: TDECU Stadium
• How to Watch (TV): ESPN
• Colorado record: 1-1
• Houston record: 2-0

Colorado vs. Houston Key Player to Watch

Ryan Staub, Quarterback, Colorado

Staub entered Colorado’s Week 2 win over Delaware and was an instant star, completing 7-of-10 passes for 157 yards and two scores, adding an 11-yard carry on the ground as well. 

A third-stringer entering the team’s Week 2 game, Staub now has a chance to win this job if Deion Sanders chooses to roll with him against the Cougars. Colorado has to take advantage of its schedule the next few weeks before it has some ranked opponents coming down the pike in October.

While Houston is favored, Colorado could be in the mix to win if Staub can repeat his play from the win over Delaware. 

Colorado vs. Houston Prediction and Pick

Houston hasn’t had to face the toughest competition to open the 2025 season, but I have a hard time backing Colorado inside a touchdown with all the uncertainty at the quarterback spot.

Sure, Staub looked great against Delaware, but can he repeat that performance against a Big 12 opponent? There's also a chance that Sanders decides to keep Salter (or a rotation of the quarterbacks) in the mix in Week 3. 

After three seasons at Texas A&M, Conner Weigman has looked solid for the Cougars in 2025, throwing for 347 yards and four scores over the first two weeks of the season. He’s likely the best quarterback that the Buffaloes will face in the first three weeks, as Haynes King threw a pick and mustered just 143 yards for Georgia Tech in a win in Week 1. 

Houston’s defense – albeit against inferior competition – has given up just nine points all season long. 

I’m buying the Cougars slowing down a Colorado attack that doesn’t seem to know which direction to go under center just yet. 

I’ll lay the points with the Cougars at home in their second season under Willie Fritz. 

Pick: Houston -4.5 (-108 at DraftKings)

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Odds refresh periodically and are subject to change.

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