Colorado vs. Wyoming prediction, odds: 2025 Week 4 college football picks, props by expert who’s up 102 units

The Colorado Buffaloes (1-2) return home to Boulder to take on the Wyoming Cowboys (2-1) on Saturday. The Buffs are looking to bounce back from a 36-20 loss against Houston in their Big 12 opener in Week 3. CU head coach Deion Sanders has yet to formally announce if Kaidon Salter or Ryan Staub will be the team’s starting quarterback, though Salter is reportedly in line to get the start. Wyoming is also coming off a blowout loss after falling to Utah 31-6 in its last outing. Colorado leads the all-time series 24-2-1.

Kickoff is set for 10:15 p.m. ET at Folsom Field in Boulder. The Buffs are 12.5-point favorites in the latest Colorado vs. Wyoming odds, while the over/under for total points scored is 45.5. Before making any Wyoming vs. Colorado picks, be sure to see what SportsLine expert Jimmie Kaylor has to say. 

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Kaylor is an NFL, college football and DFS expert for SportsLine, who has covered the NFL and college football for close to a decade as a member of the Pro Football Writers of America. His background as a former college football All-American and NFL player gives him a unique perspective when building his fantasy lineups and locking in his betting picks. He has his finger on the pulse of the college football landscape and has been cashing in big for the last two years. 

Kaylor has destroyed the sportsbooks in college football the last two seasons, posting a 240-165-7 record since Week 1 of the 2023 season. His 2024 college football futures picks included Travis Hunter winning the Heisman at 40-1 odds, bringing his net profit up to a whopping 102.86 units ($10,286.50 for a $100 bettor) since joining SportsLine as an expert in 2023. All of his picks have been featured on his SportsLine expert page or in his weekly bylined articles. Anyone who followed his picks could be way up.

Now, Kaylor has set his sights on Colorado vs. Wyoming and just locked in his picks and college football predictions. You can head to SportsLine now to see his picks. Here are several college football odds and college football betting lines for Wyoming vs. Colorado:

Why Colorado can cover

The 2025 Colorado football team, under third-year head coach Deion Sanders, is navigating a challenging season with a 1–2 overall record and a 0–1 mark in Big 12 play. The team has struggled to find consistency at the quarterback position following the departures of Shedeur Sanders and Travis Hunter to the NFL. Ryan Staub turned in a very solid performance against Delaware, and transfer Kaidon Salter is a dual-threat and a proven winner at the FBS level. 

Defensively, the team has allowed an average of 23.3 points per game. The Buffs top players on that side of the ball include linebacker Keon Colbert, who leads the team in tackles, and defensive back Tyler Harris, a key playmaker in the secondary with multiple interceptions and pass breakups. See which team to back at SportsLine.

Why Wyoming can cover

Led by second-year head coach Jay Sawvel, the Cowboys have gotten off to a 2–1 start. The Cowboys’ offense has been effective, averaging 344.7 total yards per game, including 158.7 rushing yards per game. Quarterback play has been steady, with the team spreading the ball among multiple receivers and running backs. 

Defensively, Wyoming has stayed on brand and been very solid in 2025, allowing an average of just 16 points per game and totaling 18 sacks through three games. Key defensive players include linebacker Brayden Johnson, who leads the team with three sacks, and defensive linemen Andrew Johnson, Aneesh Vyas, and Chisom Ifeanyi, each also recording three sacks. The secondary, featuring safeties Eric Richardson and Desman Hearns, along with cornerbacks Tyrese Boss and Markie Grant, has been instrumental in limiting opposing passing attacks. See which team to back at SportsLine

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How to make Wyoming vs. Colorado picks

Kaylor has analyzed CU vs. Wyoming from every angle and he’s leaning Over on the point total. He has also discovered a critical X-factor that has him jumping all over one side of the spread. He’s only sharing what it is, and which side to back, at SportsLine.

So, who wins Colorado vs. Wyoming on Saturday, and what critical X-factor makes one side of the spread a must back? Visit SportsLine now to see which side of the spread to jump on, all from the expert who is up well over 102 units since the start of 2023, and find out.