SMU vs. Louisvlle prediction, picks, odds, spread: Mustangs, Cardinals meet in top-25 clash

It's not often that one of the biggest conference games of the year is your conference opener, but that's the situation for No. 23 Louisville as it hosts No. 16 SMU in a top-25 battle that will set the stage for the rest of the ACC title race. 

SMU and Louisville have each played for the ACC Championship in the last three years and entered the 2026 season as two of the top contenders to challenge Miami for league supremacy. Unfortunately, neither SMU nor Louisville are scheduled to play Miami in the regular season this year. 

That means if either is going to beat the Hurricanes, it'll have to happen in Charlotte in the ACC Championship Game, and if Miami is there, only one spot will be up for grabs. That spot, potentially, could be hanging in the balance on Saturday afternoon in Louisville. 

The Mustangs arrive with a 2-0 record and one conference win logged in the standings after outlasting a power outage and some sloppy play to beat Florida State in Tallahassee in Week 1. They backed that win up with a victory over UC Davis that was highlighted by Kevin Jennings throwing for 337 yards and five touchdowns in one half of action, getting a game's worth of work in before letting the backups close out the 56-10 victory. This will be Jennings' third time facing Louisville as SMU's starter, and he's looking to defend not only the Mustangs' undefeated status in ACC play but also his 2-0 record against the Cards. 

SMU vs. Louisville: Need to know

Rhett Lashlee is 2-0 against Jeff Brohm as ACC foes: Two years ago, SMU came to Louisville and delivered a crushing 34-27 loss in a game where the Cards' efforts to storm back from a double-digit halftime deficit were denied. The Mustangs broke a fourth-quarter tie with an 11-play, 89-yard drive that proved to include the game-winning score. That win was part of the Mustangs' arrival not just as an ACC member but a league contender. Rhett Lashlee's crew is 15-2 in conference games since joining the league. Last season provided yet another win for Lashlee over the Cards, as SMU hosted a hobbled Louisville team that was missing its starting quarterback and top two running backs. That 38-6 win was much less dramatic in terms of game intensity, but the loss did mark three straight conference losses for Jeff Brohm and wrapped up the worst ACC record (4-4) since he took over at his alma mater. Lashlee and Brohm are regularly considered among the ACC's best coaches, but the on-field competition between the two is currently tilted in SMU's favor with two wins in the last two years.     

Lincoln Kienholz has elevated Louisville's offense: The Ohio State transfer has proven to be a perfect fit with Jeff Brohm, throwing for at least 300 yards in both games and totaling seven touchdowns (four passing, three rushing) with zero interceptions. He's the team's second leading rusher in recorded attempts (20) and team-leader in rushing yards (111) heading into Week 3, and his versatility has led to even more playmaking opportunities with more experience. After totaling just six points in the first half against Ole Miss, Louisville has logged 91 points in the following six quarters. Kienholz has showcased great chemistry with fellow portal additions Tre Richardson and Lawayne McCoy, putting them in position for success with multiple 50-plus yard touchdown passes. 

Kevin Jennings among ACC's best: Though Kienholz is an emerging star, Jennings only continues to build on his legacy as one of the SMU greats as he attempts to improve on his 21-7 record as the Mustangs' starter. He's the ACC active leader in career passing yards (8,476) and career total yards (9,072) while ranking first nationally through two games in yards per attempt (14.8) and second nationally in yards per game (383.5). SMU put together a fairly aggressive push behind Jennings for the Heisman Trophy conversation, and so far, he's backed it up. Saturday, however, could represent Jennings' best chance at a Heisman moment.  

How to watch SMU vs. Louisville live

Date: Saturday, Sept. 19 | Time: 3:30 p.m. ET Location: L&N Federal Credit Union Stadium -- Louisville, Kentucky TV: ESPN2 | Live stream: Fubo (Try for free)

SMU vs. Louisville prediction, picks

This is the back-against-the-wall spot where the Louisville coach needs to live up to the "Big Game Brohm" moniker that followed him from his days at Purdue. All three seasons have included at least one signature win, defeating Notre Dame at home in 2023, toppling Clemson in Death Valley in 2024 and knocking off then-No. 2 Miami last season. The way the schedule broke this year, Louisville has all of its big games in September. After losing to Ole Miss, the focus has to be on getting this huge ACC win. Throw in two straight losses to SMU and two years of being outside the ACC title game, and this is as must-win as it gets in Week 3.  Pick: Louisville -1.5

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