The SMU Mustangs take on the Louisville Cardinals in Louisville, Kentucky, on Saturday, Sept. 19. Kickoff is set for 3:30 p.m. ET on ESPN2.
Louisville is favored by -1.5 points on the spread with a moneyline of -128. SMU, meanwhile, enters as a +1.5 underdog and is +106 on the moneyline to pull off the upset. The over/under sits at 59.5 total points.
Here’s my SMU vs. Louisville prediction and college football pick for Saturday, September 19.
SMU vs Louisville Prediction
- SMU vs. Louisville Pick: Louisville ML (-128)
My Louisville vs. SMU best bet is on the Cardinals to win. Find the best line available on our live NCAAF odds page and be sure to download the Action Network app for more picks and analysis.
SMU vs Louisville Odds
| SMU Odds | ||
|---|---|---|
| Spread | Total | Moneyline |
+1.5 -105 | 59.5 -105o / -115u | +106 |
| Louisville Odds | ||
|---|---|---|
| Spread | Total | Moneyline |
-1.5 -115 | 59.5 -105o / -115u | -128 |
- SMU vs Louisville point spread: Louisville -1.5 (-115), SMU +1.5 (-105)
- SMU vs Louisville over/under: 59.5 (-105o / -115u)
- SMU vs Louisville moneyline: SMU +106, Louisville -128
SMU vs Louisville College Football Preview
SMU Mustangs Betting Preview: Confidence Through the Roof
The 16th-ranked Mustangs head into Saturday’s road trip to Louisville with a ton of confidence and momentum following a 2-0 start to the season.
Kevin Jennings has quickly established himself as one of the best quarterbacks in college football, throwing for 767 yards (7th) and eight passing touchdowns (3rd). He also ranks second in the country with a 95.9 QBR over SMU’s first two games.
The fifth-year starter leads an offense that also features running back Kendrick Raphael, lining up behind a veteran offensive line that does a phenomenal job of protecting Jennings in the pocket.
The Mustangs offense relies far more on Jennings’ elite arm strength and an absolutely loaded receiving corps featuring Yannick Smith and Randy Pittman on the outside, along with 5-foot-9 speedster Yamir Knight in the slot.
Fourth-year SMU head coach Rhett Lashlee is an offensive specialist, previously serving as the Mustangs' offensive coordinator before leaving to coach Miami in the same capacity.
New co-defensive coordinators Rickey Hunley Jr. and Maurice Crum Jr. feature returning linebackers Brandon Booker and Alexander Kilgore, in addition to several defensive linemen via the portal.
SMU's defense has been quite solid under its new leadership over the team’s first two games, allowing just 17 points per game and 279 yards per game.
Lashlee’s bunch has a huge test in front of them on Saturday afternoon in a true conference road game that should have vast implications for the Mustangs’ postseason aspirations.
Louisville Cardinals Betting Preview: Dual-Threat Problem
In his fourth season at the helm, Louisville head coach Jeff Brohm had some high expectations for his bunch heading into the 2026 season, looking to establish itself as a legitimate contender in the ACC.
Louisville opened the season with a close 41-38 loss to Ole Miss. It was a very solid effort in a game it nearly won down the stretch versus a top-10 opponent.
The Cardinals got right back on track last week in their home opener, absolutely thrashing Villanova, 59-14, in what should give Brohm’s team confidence and momentum heading into Week 3’s ACC showdown with SMU.
Ohio State transfer quarterback Lincoln Kienholz has been unbelievable in his first season with Louisville, throwing for 639 yards and four scores in the Cardinals’ first two games.
The former Buckeye has yet to turn the ball over this season and enters Saturday’s conference matchup with the fourth-best QBR in the entire country at 91.7.
Kienholz boasts exceptional versatility under center as a legitimate dual-threat QB who has already rushed for 111 yards with three touchdowns. He leads a rushing attack that also features running backs Isaac Brown and Keyjuan Brown.
The Cardinals offense features a diverse, pro-style scheme that relies heavily on shotgun, pistol and singleback sets, which have already given opposing defenses fits as a result of Kienholz's tremendous playmaking ability in the pocket.
Brohm frequently utilizes two-tight-end formations out of both the gun and the pistol to add further strength to Louisville’s elite rushing attack.
The Cardinals also excel on the defensive side of the football, frequently using a 4-2-5 scheme featuring two edge rushers and two interior linemen to control gaps and pressure opposing QBs, with Clev Lubin and Jerod Smith II leading the charge.
Hybrid defensive playmaker Antonio Watts has also played a massive role in the Cardinals’ defensive efficiency at the STAR position, playing alongside four other defensive backs in their secondary.
It will take a grand effort on both sides of the football for Louisville to come out victorious, especially against an electric SMU offense led by Jennings.
SMU vs Louisville Pick, Betting Analysis
We're in for an absolute showdown on Saturday afternoon in a ranked ACC clash that will, in all likelihood, be one of the best matchups on Week 3’s college football slate.
From a betting perspective, it's tough to ignore how impressive Jennings has been over the Mustangs’ first two contests. He has definitively established himself as one of the nation’s best signal-callers.
Jennings has been sacked just once all season and has been pressured on just 19% of his dropbacks, which ranks near the top of the entire country.
That said, I don't think this Mustang defense has been tested yet. It now has a massive step up in competition, going on the road to Louisville to face a quarterback who's one of the most versatile players in college football.
While Saturday’s ACC matchup is fairly close to a coin-flip, just as the betting odds project, I slightly favor the home Cardinals in what I expect to be a legacy-defining performance from Louisville’s dual-threat phenom.
Pick: Louisville ML (-128)
SMU vs Louisville Betting Trends
