Game day is officially here! Louisville football is set to take on the Ole Miss Rebels in what is the only ranked-vs.-ranked matchup in Week 1. The Cardinals are ranked in Week 1 for the first time since 2017, and they will look to rewrite history, as they have never beaten a ranked opponent in Week 1.
Louisville is 0-7 against ranked teams in Week 1, including losing five of those games by 17 or more, according to Greg McElroy. However, this time, Louisville has Jeff Brohm leading the team, and since Brohm has been at Louisville, the Cardinals have proven they can win big-time games, including last year when they defeated No. 2 Miami, who beat Ole Miss in the CFP semifinals.
The Cardinals are eyeing their first-ever ACC Title and first-ever College Football Playoff berth, and if they can find a way to upset No. 9 Ole Miss, it would be a massive step in the right direction. So now that the stakes are set, let’s break down the final odds for huge season-openers and make some predictions
Betting odds for Louisville vs. Ole Miss
Odds courtesy of FanDuel, and as of 6am ET on Saturday, September 6th.
Spread: Ole Miss -6.5
Over/Under: 54.5
Moneyline: Ole Miss -250 Louisville +205
Big Red Louie Predictions
The time has finally come. Louisville football is back, and they have a monster Week 1 opponent. The Rebels are coming off a historic year where they made their first-ever CFP, defeated Georgia in the quarterfinals, and reached the semifinals after winning a program-record 13 games in one season.
The Cardinals will try to upset the No. 9 Ole Miss, and while not many are picking Louisville, they do have a real chance. Brohm has upset a top-15 team in the country for three straight years, including No. 10 Notre Dame in 2023, No. 11 Clemson in 2024, and No. 2 Miami in 2025. If Louisville wants to win this game, it will come down to its quarterback, Lincoln Kienholz, and its offensive line.
Kienholz has never started a game in college football, and while this offensive line has experience, it was rebuilt from the portal and has yet to play a snap together. There is a lot of upside with Kienholz and this offensive line, but it is definitely a tall order to ask them to make their debut against this elite Ole Miss team.
For those two key x-factors, we're leaning Ole Miss in this showdown. The Rebels' defensive line returns some heavy hitters in Will Echoles and Suntarine Perkins, who combined for 149 tackles and 9.5 sacks last year. And on offense, they, of course, return Heisman candidate Trinidad Chambliss and preseason All-American Kewan Lacy.
So, the Rebels' experience is what has us leaning Ole Miss, but if this offensive line can win the trenches as it did against Miami, and if Kienholz can limit mistakes and turnovers, the Cardinals can certainly pull off this upset. But for now, we are going with Ole Miss.
Prediction: Ole Miss 31 Louisville 24
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