Since joining the FBS, the James Madison Dukes have quickly become one of the most popular and successful Group of Five programs. However, casual fans might not realize that a step back could be coming in 2025.
They’re clearly not on the same level as the Louisville Cardinals, and my James Madison vs. Louisville predictions break down why backing the favorite is the smart move here.
Read all about it in my college football picks for September 5.
James Madison vs Louisville prediction
James Madison vs Louisville best bet: Louisville -13.5 (-105)
Since joining the FBS in 2023, the James Madison Dukes have gone 8-3, 11-2, and 9-4, and are once again one of the favorites to win the Sun Belt.
However, success for a Group of Five program in the NIL and transfer portal era can mean your roster gets pillaged by bigger programs. While QB Alonza Barnett returns, the Dukes must replace 12 starters.
JMU looked impressive vs. FCS Weber State, but Louisville provides a completely different challenge.
This is Jeff Brohm’s best team since he came to Louisville. The Cardinals have talent, depth, and experience, while returning 16 starters — including the dynamic running back duo of Isaac Brown and Duke Watson.
One of the new faces is under center. Brohm brought in former USC QB Miller Moss to lead the offense, who threw for 2,555 yards with 18 touchdowns and nine interceptions before losing his starting job last season.
Moss is good enough to make you respect the Cardinals' pass game, and then watch them run all over you just like they did against FCS Eastern Kentucky in Week 1.
This might be the best team James Madison has faced since joining the FBS in 2023. The talent discrepancy will become apparent as the game progresses. Don’t overthink this and lay the points with Louisville.
James Madison vs Louisville same-game parlay
It will just be a productive night for the Cardinals all around. With Moss at quarterback, this is a balanced offense, but running the football remains their bread and butter.
Isaac Brown is a stud. He rushed for 1,173 yards at 7.1 yards per carry and 11 scores last season, picking up right where he left off, going for 126 yards and two touchdowns on just six attempts in the season-opening win over EKU. I like him to top the century mark once again.
Moss did his part too, throwing for 223 yards in basically just one half of action. He should play a little more on Friday night and top his passing yard prop of 250.5.
James Madison vs Louisville same-game parlay
- Louisville -13.5
- Isaac Brown Over 99.5 rushing yards
- Miller Moss Over 250.5 passing yards
Our deep-ball SGP: Hello offense
- Brown is a home run hitter who can take it to the house on any play.
- He scored 11 rushing TDs last season.
- The offense runs through Brown, so he's a great bet to score the first TD of the game.
James Madison vs Louisville same-game parlay
- Louisville -13.5
- Isaac Brown Over 99.5 rushing yards
- Miller Moss Over 250.5 passing yards
- Isaac Brown to score FIRST touchdown
James Madison vs Louisville game predictions
James Madison vs Louisville moneyline prediction
Louisville is winning this football game. It has an edge in talent, depth, and experience, and this game is in Louisville.
James Madison vs Louisville spread prediction
Those edges will show as the game moves into the second half. The Cardinals' ground game will wear on the Dukes and allow Louisville to extend its lead and cover this two-touchdown spread.
James Madison vs Louisville Over/Under prediction
Both teams are run first when it comes to offense. And with at least one good defense on the field, the clock could constantly be moving. I'd lean toward the Under.
James Madison vs Louisville odds
- Spread: James Madison +13.5 | Louisville -13.5
- Moneyline: James Madison +375 | Louisville -500
- Over/Under: Over 55.5 | Under 55.5
James Madison vs Louisville trend to know
Louisville has hit the game total Over in nine of its last 13 games for +4.60 Units and a 32% ROI. Find more college football betting trends for James Madison vs Louisville.
How to watch James Madison vs Louisville
| Location | L&N Federal Credit Union Stadium, Louisville, KY |
| Date | Friday, September 5, 2025 |
| Kickoff | 7:00 p.m. ET |
| TV | ESPN2 |
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Odds are correct at the time of publishing and are subject to change.
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