College Football Upset Picks for Week 1 (Bet Louisville to Upset Ole Miss)

The good news is that Week 1 of the college football season is here. The bad news is that this week is used by most teams as a warm-up for the upcoming season, scheduling a team from a far worse conference to give them an easy win in the first week.

That has led to almost every game having lopsided betting odds, with many games not even having moneyline odds available to bet due to there being virtually no chance of an upset taking place.

With that being said, there are still a few upset spots I like for Week 1. We went 1-1 with my upset picks in Week 0, so let's keep the momentum going.

College Football Week 1 Upset Picks

Odds via Caesars Sportsbook

Wyoming +135 vs. Colorado State
Louisville +215 vs. Ole Miss
California +106 vs. UCLA

Wyoming vs. Colorado State Prediction

The only unit in this game that had a strong 2025 season was the Wyoming defense. The Cowboys ranked 18th in defensive success rate and 32nd in opponent EPA per play. Meanwhile, Colorado State ranked outside the top 100 in almost every single offensive and defensive metric you can find.

Wyoming's roster may have some turnover, but Jay Sawvel is back as their head coach, so I expect, at the very least for this team to once again be strong on the defensive side of the ball. That's enough for me to bet on them as a road underdog in Week 1.

Pick: Wyoming +135

Louisville vs. Ole Miss Prediction

Trinidad Chambliss is back for another year at Ole Miss, but that's not enough for me to think that the Rebels will be the dominant team they were last season under Lane Kiffin. There's no doubt that Ole Miss has plenty of offensive weapons, but so does Louisville. Isaac Brown, the Cardinals' running back, averaged a blistering 8.8 yards per carry last season. If he can replicate numbers even close to his 2025 production, Louisville is going to be a tough offense for any defense to stop.

Let's also remember how good this Louisville defense was last season, ranking 25th in the country in defensive success rate, compared to Ole Miss, which ranked 56th in that metric while ranking 86th in opponent rush success rate.

I have more faith in the team with the returning head coach. This could be a big season for Jeff Brohm.

Pick: Louisville +215

UCLA vs. California Prediction

In my full betting preview for this game, I made the case for betting on UCLA to pull off the upset:

If UCLA had impressive metrics from a year ago, the fact that they are returning a bulk of their production would make me hopeful, but unfortunately, that's not the case. Their advanced metrics were horrible a year ago, ranking 116th in Net EPA per Play, 87th in offensive success rate, and 134th in defensive success rate.

California went out and improved its roster with the transfer portal and then, more importantly, hired Josh Lupoi as its head coach. I have high hopes for Lupoi as a head coach, having just coached one of the best defenses in the country at Oregon.

I'll bet on California to pull off the upset as small underdogs in this one.

Pick: California +106

Follow Iain on X and Instagram

Bet $1, get 100% profit boost on your next 10 bets when you claim your Caesars Sportsbook new user promo using code ‘SICZRDYW’. Sign up, deposit at least $10, and place your first real-money wager. Up to $25 max bet per boost.

Odds refresh periodically and are subject to change.

If you or someone you know has a gambling problem and wants help, call 1-800-GAMBLER.

You can check out all of Iain's bets here!

Add us as a preferred source on Google