Louisville gets its shot at rewriting a brutal Week 1 trend when it opens against No. 9 Ole Miss in the only ranked-vs.-ranked matchup of the opening weekend.
The Cardinals are back in the Week 1 rankings for the first time since 2017, but the history book is not exactly on their side. Louisville is 0-7 against ranked teams in Week 1, and five of those losses came by 17 points or more, according to Greg McElroy.
Still, this isn’t the same Louisville program that has been trying to claw its way into relevance for years. Jeff Brohm has already shown he can deliver in big moments, and since arriving in Louisville, he has helped the Cardinals knock off marquee opponents, including No.
2 Miami last season.
That win matters here because Miami went on to beat Ole Miss in the CFP semifinals, and Louisville is trying to use this opener as another step toward bigger goals. The Cardinals are chasing their first ACC title and their first College Football Playoff berth, and taking down the Rebels would give that push real momentum.
Ole Miss, though, comes in with a résumé that demands respect. The Rebels are coming off a landmark season in which they reached the CFP for the first time, beat Georgia in the quarterfinals and finished with a program-record 13 wins.
On the betting side, FanDuel has the over/under set at 54.5.
The matchup also comes down to a couple of obvious pressure points for Louisville. If the Cardinals are going to pull this off, Lincoln Kienholz and the offensive line have to hold up.
Kienholz has never started a college game, and the line was rebuilt through the portal, meaning this group is still learning how to function together in live action. That’s a tough ask against an Ole Miss front that returns Will Echoles and Suntarine Perkins, who combined for 149 tackles and 9.5 sacks last year.
Ole Miss also brings plenty back on offense, with Heisman candidate Trinidad Chambliss and preseason All-American Kewan Lacy leading the way.
Brohm has made a habit of knocking off top-15 teams, doing it in three straight years with wins over No. 10 Notre Dame in 2023, No.
11 Clemson in 2024 and No. 2 Miami in 2025.
That gives Louisville a real puncher’s chance. If the rebuilt line can control the trenches the way it did against Miami and Kienholz keeps the ball out of harm’s way, the Cardinals can absolutely make this interesting.
But with Ole Miss’ experience on both sides of the ball, the lean here is the Rebels.
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