We have a banger out of the gate, as the No. 24 Louisville Cardinals visit No. 9 Mississippi — the only matchup featuring two Top 25 teams in Week 1.
Prediction markets favor the Rebels, who are trading at 72¢ to win outright (implying a 72% probability), powered by arguably the best offensive backfield in football. Mississippi is favored by 6.5 points on the spread with a total of 55.5.
Read below for my early Louisville vs Mississippi predictions and college football picks for Sunday, Sept. 6.
Louisville vs Mississippi predictions
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Percentages courtesy of Kalshi, one of the best prediction market apps.
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Early Louisville vs Mississippi spread pick: Mississippi -6.5
Continuity is the edge for Mississippi, which returns QB Trinidad Chambliss and RB Kewan Lacy from a CFP quarterfinal team that averaged 36.9 points last season. New OC John David Baker should maintain its up-tempo attack.
Louisville, meanwhile, returns just nine players who logged significant snaps, including first-time starter Lincoln Kienholz.
His debut comes against a Rebels' front seven that helped them rank fifth nationally in passing yards allowed.
The experience and continuity gap favors Mississippi.
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Early Louisville vs Mississippi total pick: Over 55.5
Louisville has the pieces for a dynamic offense, and even if QB Lincoln Kienholz struggles, the Rebels should do enough heavy lifting to push this Over.
Kienholz should lean on running back Isaac Brown, who averaged 8.8 yards per carry last season, while Keyjuan Brown and Missouri transfer Marquise Davis add explosiveness.
That’s a tough matchup for a Mississippi defense that ranked Bottom 5 against the run, allowing nearly 150 yards per game.
Louisville should find enough success on the ground to keep pace, while the Rebels’ offense supplies the rest.
I’d play the Over up to 57.5 points.
Louisville vs Mississippi odds
- Louisville vs Mississippi spread: Mississippi -6.5
- Louisville vs Mississippi moneyline: Louisville 28%, Mississippi 72%
- Louisville vs Mississippi Over/Under: 55.5
How to watch Louisville vs Mississippi
- Louisville vs Mississippi matchup
- Date: Sunday, Sept. 6, 2026, 7:30 p.m. ET
- City: Nashville, TN
- Venue: Nissan Stadium
- TV: ABC
Odds are correct at the time of publishing and are subject to change.
Not intended for use in MA.
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