The Colorado Buffaloes return home in Week 4 looking to steady their season against the Wyoming Cowboys in a regional clash that carries plenty of intrigue. With Kaidon Salter back under center after a brief benching, Colorado hopes to reestablish consistency on offense, while Wyoming looks to grind out another physical performance and test the Buffaloes’ ability to cover as a heavy favorite.

Our full Wyoming vs. Colorado predictions break down the spread, odds, and best betting angles, along with how to watch the game and where to claim an instant $200 bonus from Bet365.

Wyoming vs. Colorado Predictions For College Football Week 4, Saturday, 9/20

Colorado enters Week 4 as a -12.5 point favorite at home after losing to Houston by 16 points, but the team hasn’t always looked comfortable in 2025. Quarterback Kaidon Salter began the season as the starter before being briefly benched, only to regain the job after Ryan Staub struggled. Salter’s dual-threat ability gives the Buffaloes their best chance to generate explosive plays, but he’ll need to avoid turnovers against a Wyoming team that thrives on limiting mistakes.

Wyoming comes into this matchup knowing exactly who they are. The Cowboys play a physical, run-heavy brand of football, aiming to control time of possession and wear down opposing defenses. That style could frustrate Colorado, particularly if the Buffaloes start slow or fail to finish drives in the red zone. Also, Colorado’s run defense hasn’t been great historically; they will have to sell out in order to stop the run and trust their defensive backs to win 1-on-1 matchups.

While Colorado has the talent advantage, Wyoming’s approach makes it dangerous as a double-digit underdog. If Salter gets in rhythm early, Colorado can separate, but if Wyoming dictates pace, this game could be closer than the odds suggest.

Wyoming vs. Colorado Spread Pick/Best Bet

Pick: Wyoming +12.5

Colorado should have enough to win this game outright, but covering -12.5 feels like too much to ask given their recent inconsistency on offense. Wyoming’s defense is solid enough to keep the Buffaloes from running away with it, and their ground game is designed to shorten contests and limit possessions.

Backing Wyoming +12.5 looks like the stronger play. Expect Colorado to win, but by single digits rather than two touchdowns.

 

 

 

How To Watch Wyoming vs. Colorado College Football Week 4

  • Date: Saturday, September 20, 2025
  • Kickoff time: 10:15 PM EST
  • Location: Folsom Field — Boulder, CO
  • TV broadcast: ESPN / ESPN2 (check local listings)
  • Streaming options: ESPN app, ESPN+ with provider login

Fans across the country will be able to tune in, with the game expected to draw attention thanks to Colorado’s quarterback storyline and Wyoming’s upset potential; however, it will be a late one for Parents' weekend in Boulder.

Wyoming vs. Colorado Odds, Spreads, Total & Betting Lines

Here are the current lines ahead of Saturday night’s kickoff:

  • Point spread: Colorado -12.5 (-110) | Wyoming +12.5 (-110)
  • Moneyline: Colorado -480 | Wyoming +350
  • Total (Over/Under): 53.5 points

These odds reflect sportsbooks expecting Colorado to bounce back at home, but bettors backing Wyoming see value in their ability to keep the game competitive. The total suggests a moderate-scoring game, with oddsmakers weighing Colorado’s explosiveness against Wyoming’s slower pace.

 

 

 

Wyoming vs. Colorado Injury Report & Latest News

Colorado updates

  • Quarterback: Kaidon Salter has been reinstated as the starter after Ryan Staub struggled in Week 3. His dual-threat skillset is key to Colorado’s offensive rhythm.
  • Offensive line: Colorado’s protection remains a concern. Keeping Salter upright will be a major factor in whether they can cover the spread.
  • Defensive health: No major new injuries reported, but the defense will be tested against a heavy run attack.

Wyoming updates

  • Running back rotation: Wyoming leans on a deep stable of backs to move the chains and control the clock. They’re expected to be healthy heading into this game.
  • Defensive front: This group has been the strength of the team, and they’ll need another strong showing to slow down Salter’s mobility.
  • No significant injuries reported as of early week preparation.

How To Bet on Wyoming vs. Colorado at Bet365 Sportsbook & Claim Your $200 Bonus

You can wager on Wyoming vs. Colorado with Bet365 and grab one of the best new-user promos available. Here’s how:

  1. Sign up at Bet365 Sportsbook with this link (must be in a state where it’s legal).
    1. AZ, CO, IA, IL, IN, KS, KY, LA, NC, NJ, OH, PA, TN and VA
  2. Deposit at least $5 into your new account.
  3. Place your first $5 wager on Wyoming vs. Colorado — spread, moneyline, or total.
  4. Regardless of the outcome, you’ll unlock $200 in bonus bets guaranteed.

This promo gives you extra flexibility to bet not only on this matchup but also roll over some of the bonus into NFL’s Week 3 slate on Sunday.

 

Â