Deion Sanders and the Colorado Buffaloes aim to climb back to .500 when they host the Wyoming Cowboys tonight.
Wyoming hung with Utah for a half last week before getting blown out, and now faces a Colorado squad still searching for answers at quarterback.
Find out why fatigue and the mile-high altitude give the Buffs an edge in my Wyoming vs. Colorado predictions and college football picks for Saturday, September 20.
Kickoff is set for 10:15 p.m. ET from Folsom Field in Boulder, with the game airing on ESPN.
Wyoming vs Colorado prediction
Wyoming vs Colorado best bet: Colorado -13.5 (-110)
The Wyoming Cowboys held Utah to just three points in the first half last week, but that is a bit misleading on the surface. The Utes missed three field goals and surrendered a fumble inside the five-yard line.
The Utes simply executed better after halftime, putting up 28 points. In the process, they ran the ball for 311 yards on 45 carries in addition to 230 passing yards.
The Colorado Buffaloes are operating with an extra day of rest, and that will give the home team an additional advantage over the banged-up and exhausted Cowboys. And regardless of who's playing quarterback, the path to victory is as simple as running the ball.
Simeon Price has only carried the ball 19 times, but he’s averaging better than seven yards per carry. Kaidon Salter is expected to return to the starting lineup, and he can take off at any time — and has often had to do so due to poor blocking on passing plays.
Micah Welch hasn’t gotten on track as the team’s leading rusher in terms of carries. But this could be the game, taking on a Wyoming defense ranked 113th in success rate on rushing plays and allowing 3.3 line yards per rush.
The Buffaloes have had success when running the ball for the most part, with an explosive run rate of over 12%. They picked up 146 yards against Georgia Tech, and I expect we’ll see them commit to it here with the struggles at the quarterback position.
Wyoming has the 90th-ranked offense in terms of EPA/play according to GameOnPaper, after adjusting for opponents faced. The Cowboys managed just 10 points against an Akron team that surrendered 68 to Nebraska and 31 to UAB.
This game will get away from the Cowboys as fatigue and elevation eventually take their toll. Colorado will win comfortably, something I doubt we’ll say again this season.
Wyoming vs Colorado same-game parlay
I will honestly be surprised if Wyoming scores 10 points in this game. The Cowboys rank 95th or worse in EPA/pass, first down success, and offensive EPA/play. They’re also allowing a stuff rate of 24%, and have scored just 2.9 points per quality possession.
One thing Wyoming has done well is prevent big pass plays, and Colorado’s instability at QB will likely limit those. I see the Buffaloes getting to around 31 to 34 points, nowhere near enough to go Over.
I’m expecting the third quarter to be when the game really breaks open. Wyoming has scored just seven points across its three third quarters, and Utah scored a pair of touchdowns after the break last week.
The fatigue and altitude will begin to show up after the intermission, and the Buffaloes will score at least one touchdown in the third stanza.
Wyoming vs Colorado 3-leg SGP
- Colorado -13.5
- Under 44.5
- Colorado 3Q -3.5
Wyoming vs Colorado game predictions
Wyoming vs Colorado moneyline prediction
Colorado hasn’t been good, but it would be a monumental upset for the home team to lose this game. Wyoming’s offense is beyond anemic, averaging just 245 yards against two FBS opponents. The Buffaloes will get the victory.
Wyoming vs Colorado spread prediction
As we’re taking Colorado to cover the spread, it’s clear that I’m backing them to cover the 13.5-point number. Check above for analysis!
Wyoming vs Colorado Over/Under prediction
The Cowboys rank 95th or worse in EPA/pass, first down success, and offensive EPA/play. They’re also allowing a stuff rate of 24%, and have scored just 2.9 points per quality possession.
Wyoming vs Colorado odds
- Spread: Wyoming +13.5 | Colorado -13.5
- Moneyline: Wyoming +375 | Colorado -500
- Over/Under: Over 45.5 | Under 45.5
Wyoming vs Colorado trend to know
The Under has cashed in six straight Wyoming games, dating back to November 2024. Find more college football betting trends for Wyoming vs Colorado.
How to watch Wyoming vs Colorado
| Location | Folsom Field, Boulder, CO |
| Date | Saturday, September 20, 2025 |
| Kickoff | 10:15 p.m. ET |
| TV | ESPN |
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