James Madison Dukes vs Louisville Cardinals Prediction, Odds and Picks for Friday, 09/05/25

Following a couple of easy victories in Week 1, both James Madison and Louisville will get its first real test of the season on Friday in a game that could sneakily end up having major College Football Playoff implications. After all, James Madison should be looking to follow the Boise State model from a season ago and just keep this one respectable for the playoff committee to recognize that it was a “quality loss”. That’s the name of the game these days, and I’m of the belief that the Dukes will be able to keep this one within the number.

For my money, James Madison was the clear standout in the Sun Belt back when I wrote up the conference preview last month, and my opinion certainly hasn’t changed after watching the Dukes throttle Weber State in Week 1. What makes Bob Chesney’s team so difficult to prepare for is that they’ll be using multiple quarterbacks in this game, as second year starter Alonza Barnett III got the majority of the workload through the air last week, while I expect Matthew Sluka to get at least 10 carries and be more involved through the air as well. The Dukes likely kept things pretty vanilla on offense last week, but this is a deep and experienced unit that has no trouble playing against Power 4 competition, as we saw against North Carolina a season ago.

On the other side, Louisville is a team I’m fairly high on from a season-long perspective, but the Cardinals were far from perfect against Eastern Kentucky last weekend, turning the ball over 3 times and committing a whopping 12 penalties for 106 yards in the victory. It remains to be seen just how quickly Miller Moss can pick up Jeff Brohm’s offense and while Louisville should find some success in this game, I don’t think it’ll be as easy as the market is signifying given that James Madison has a very experienced defense that could start as many as 7 seniors in this contest. If the Louisville offenses continues to struggle on late downs (77th in 3rd/4th down success rate), the Dukes should be able to keep this one within two touchdowns.

James Madison vs Louisville prediction: James Madison +14.5 available at time of publishing. Playable to +14. 

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