James Madison vs Louisville Prediction, Picks & Odds for September 5 — College Football Week 2

James Madison has had success since joining the FBS, but the Dukes will be no match for the Louisville Cardinals in Week 2.

Andrew Caley - Senior Betting Analyst at Covers.com
Andrew Caley • Senior Betting Analyst
Sep 4, 2025 • 08:46 ET • 4 min read

NCAAF

Match starts: 30 hrs
LOU
58 %
JMU
42 %
EXPERT PICK - SPREAD
Louisville -13.5 (-105) Louisville -13.5 (-105)
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Louisville Cardinals running back Isaac Brown (1) runs the ball against Eastern Kentucky Colonels defensive back Rishad Hence.
Photo By - Imagn Images. Louisville Cardinals running back Isaac Brown (1) runs the ball against Eastern Kentucky Colonels defensive back Rishad Hence.

The James Madison Dukes have become one of the most popular and successful Group of Five teams since joining the FBS, but casual fans might not realize the Dukes could take a step back in 2025.

They certainly aren’t on the same level as the Louisville Cardinals, and my James Madison vs. Louisville predictions explain why you shouldn’t overthink backing the favorite.

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.

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 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.
Not intended for use in MA.
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Andrew Caley
Senior Betting Analyst

When his dreams of becoming the next Steve Nash died, all Andrew "Taco" Caley wanted to do was write about sports, something he's been doing at Covers for more than a decade. A Journalism School grad from Holland College in Charlottetown, PEI, Andrew previously worked at The Chronicle Herald and Star Metro, but knew in his heart that his future lay in sports. He began at Covers as a news editor and has now done everything under the sun when it comes to content. His work has been seen on TSN, Sportsnet, VSiN, and CBS. These days Andrew's betting expertise is focused on his favorite teams; the Toronto Blue Jays and Toronto Raptors. He's also an avid college football fan and bettor. He can't be friends with you if you don't appreciate a Service Academy Under. The sportsbook where he does the bulk of his betting is bet365 thanks to its numerous prop betting options and competitive odds. His best advice? Find the balance between the numbers and what you see on the playing field. Then find the best price using multiple books. And don’t ask him where the nickname Taco comes from. It's not an interesting story. Seriously.

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