College Football Week 1 Best Bets: Sunday, September 6
The college football season fully begins in earnest this weekend and that includes a Sunday slate that features a couple of fascinating matchups. With another day of entertaining college football action ahead of us, it’s time to get into the remainder of the Week 1 slate with the return of my weekly CFB best bets column. We got off to a 2-0 start in the column in Week 0, and the good vibes kept coming as I cashed both of my best bets on Thursday's card and finished 2-1 on Saturday's slate. Let's keep the momentum going!
With the Saturday slate behind us, it's time to turn our attention to Sunday's smaller card card. Let’s take a look at my CFB best bets for today, while you can also find all of our expert CFB picks for this weekend’s action and every FBS game throughout the year.
CFB Best Bet: Louisville Cardinals +7 vs Ole Miss Rebels (-120)
Odds available at Fanatics Sportsbook at time of publishing. Playable to Louisville +6.5 (-105)
I don't have a strong opinion on either of the first two games on Sunday's slate, but I do generally echo my colleague Sam Avellone's thoughts on Notre Dame's expected dominance against Wisconsin. I generally lean toward the under in that contest, and the same can be said for what we can expect in this SEC vs. ACC matchup — especially if the game script favors the underdog Cardinals and how they'll likely want to attack the Ole Miss defense.
To their credit, the Rebels were able to respond valiantly to Lane Kiffin's departure and win multiple College Football Playoff games last season — even coming within just a few plays of making the title game. However, this season is when the true loss of Kiffin and former offensive coordinator Charlie Weiss Jr. should come into play. It's hard to ignore the talent of Trinidad Chambliss and Kewan Lacy as a backfield duo -- I fully understand why this offense enters the season with such high expectations -- but part of Chambliss' incredible success in 2025 was his extraordinary downfield passing numbers, and that's not something that is easily replicable on a consistent basis. Elsewhere, while Ole Miss appears to have landed a rock solid transfer portal class, the wide receiver room took a pretty significant step back, and I'd expect the Rebels to rely more on their ground attack in this one against an experienced Louisville defense that should be stout up front and ready to stuff the run.
I'm not high on Pete Goulding and John David Baker as head coach and offensive coordinator respectively, but I would've been all over Louisville in this spot regardless of who was on the Rebels sideline. This is a play on Jeff Brohm, who has been an excellent coach as an underdog historically. Not only is Brohm 11-4 against the spread as an underdog of 7+ points since 2018, he's won 6 of those games outright — with many of those upsets coming as a double-digit underdog. Brohm typically shines in this role, especially when given this much time to prepare.
With Louisville reportedly implementing an entirely new run-based offense around new quarterback Lincoln Kienholz and their excellent running back Issac Brown, this is an ideal spot for the Cardinals to catch Ole Miss in the first regular season game of the Goulding era. Ultimately, the element of surprise and a real coaching edge favors Louisville on Sunday, so I'll back the Cardinals to keep things within a touchdown.
Don't miss our expert's full analysis for our Louisville vs Ole Miss prediction
College football Week 1 predictions
If you're looking for more college football predictions today, check out the rest of our picks for Week 1:
