Eastern Kentucky Colonels vs Louisville Cardinals Prediction, Odds and Picks for Today, 08/30/25

The Louisville Cardinals enter a new era with USC transfer Miller Moss taking over at quarterback. Entering the season as a fringe top-25 team that ranked 13th in total offense and 9th in scoring offense a year ago, the Cardinals are stacked at skill positions and should have no issue carving through an FCS defense. For starters, Louisville returns one of the best WR duos in the ACC in All-Conference selection Chris Bell alongside Caullin Lacy. Furthermore, you could make a case that the Cardinals have a top-3 running back in the country as Isaac Brown returns from a 1,173-yard season on the ground with 11 touchdowns. The one-two punch in the backfield is completed with Duke Watson, who finished with 8.91 yards per carry in 2024. 

Defensively, Louisville was average at best in 2024. They lost talent, and brought in several talented transfer players to make up for that lost production. There could be some growing pains on the defensive side of the ball, but I don’t expect that to shine through until the Cardinals reach ACC competition. For what it’s worth, Louisville covered a 39.5 point spread in a 62-0 win over their lone FCS opponent — Austin Peay — in 2024 and I wouldn’t be surprised if we saw a similar result to begin the new season. With all things considered, the talent gap is simple too wide and I’ll take the Cardinals to begin the season 1-0 with a blowout win at home.

Eastern Kentucky vs Louisville prediction: Cardinals -38.5 (-110) available at time of publishing. Playable at that number or better.

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