SMU vs Louisville Predictions, Odds and Picks for Saturday: Offense Expected in Derby City

For the past two years, the SMU vs. Louisville matchup has been one the Cardinals would rather not have seen.

Since the Mustangs joined the ACC in 2024, they’ve made life tough on Louisville. SMU won its first trip to Louisville by a touchdown, on its way to a perfect 8-0 run through the ACC regular season. Last year, having just fumbled away its chance to take control of the league against Clemson, Louisville got its doors blown off, falling 38-6 to the Mustangs in Dallas.

This time around, the matchup is even more significant. Neither SMU nor Louisville plays Miami, and both will probably be favored to win every conference game for the rest of the season. That means a win here puts the victor in the driver’s seat for a trip to Charlotte. While both teams might have the resume for the College Football Playoff by that time anyway, a win there would mean an automatic bid to the tournament.

With a loss, there might not be enough time to recover. Even though it’s only September, the ACC appears so top-heavy that two losses might be enough to knock a team out of the race. With Miami not expected to lose to anyone, neither side believes it has any margin for error here.

That’s not a great spot to be for either defense. The Mustangs and the Cardinals have both struggled on that side of the ball, in part because they’ve opened by facing decent offenses.

They’re in that same situation again, as SMU’s offense has the best unit on the field and Louisville’s offense held its own with Mississippi. This matchup looks like two teams who know how to put up points, making a high-scoring affair likely in round 3 of SMU vs. Louisville.

SMU vs. Louisville Prediction

Best Bet: SMU Team Total Over 28.5 (BetMGM, -108)

The total won’t be easy to reach. SMU is the more likely of the two to reach it for three reasons.

First, the Mustangs have the more experienced quarterback in Kevin Jennings. Jennings has topped 300 yards in each of his first two games, and the Louisville secondary has been shredded this season. The Cardinals rank 118th in the country against the pass, and while part of that comes from playing Mississippi, they gave up a 65-yard passing touchdown last week to Villanova.

The Mustangs have the personnel to see those spots and take full advantage of them. More importantly, they’ve had a chance to clean up the mistakes they made in Tallahassee. Conditions should be much better than they were against Florida State, which should lead the offense to look more like it did against Cal-Davis.

Finally, Louisville’s offense is good enough to go toe-to-toe with the Mustangs. That means Jennings will have every incentive to keep throwing. He’s not going to be able to sit back and play with a comfortable lead; he’ll have to keep putting up points to keep SMU in front. That leads to plenty of back-and-forth, which should mean the Mustangs give the scoreboard a workout.

Up To $1500 in Bonus Bets Paid Back if your First Bet Does Not Win

Bet Now BetMGM Promo

Gambling problem? Call 1-800-GAMBLER or 1-800-MY-RESET (Available in the US) 877-8-HOPENY or text HOPENY (467369) (NY) 1-800-327-5050 (MA), 1-800-BETS-OFF (IA), 1-800-981-0023 (PR). 21+ only. Please Gamble Responsibly. See BetMGM.com for Terms. First Bet Offer for new customers only (if applicable). Subject to eligibility requirements. Bonus bets are non-withdrawable. In partnership with Kansas Crossing Casino and Hotel. Promotional offers not available in Mississippi, Massachusetts, New York, Ontario, or Puerto Rico.

170,000 GC + 7 SC

Play Now Sportzino Promo

T&Cs apply, 18+

SMU vs. Louisville Same Game Parlay (+602, BetMGM)

• Over 58.5

• Kevin Jennings Over 275.5 Passing Yards

• SMU +1.5

The line is the toughest part to pick for SMU vs. Louisville. The teams appear to be even, as Lincoln Kienholz has stepped into Jeff Brohm’s offense and managed things well. Louisville shouldn’t get knocked out of the game early like last year, which should keep the points coming.

The problem is that lately, Brohm’s title of “Big Game Brohm” feels more like a mockery than a boast. The Cardinals have fumbled away multiple games that they had no business losing over the past two seasons. Last year against Clemson, Louisville missed two field goals and lost 20-19 to Dabo Swinney’s weakest Tiger team in years.

The Cardinals haven’t shown they can win these kinds of games lately. The Mustangs have. The experience should serve them well.

How to Watch SMU vs. Louisville

Location: L&N Federal Credit Union Stadium, Louisville, Ky.

Date: September 19, 2026

Time: 3:30 p.m. Eastern

TV: ESPN2