#16 SMU vs. #23 Louisville Prediction, Spread, NCAAF Picks – Saturday, September 19

Week 3 of the college football season doesn’t feature many marquee matchups, but #16 SMU and #23 Louisville will square off in a ranked ACC showdown on Saturday, September 19, at 3:30 p.m. ET on ESPN2. Louisville enters Saturday as slight 1.5-point home favorites over their conference foes on PrizePicks.

After a three-point victory over Florida State in Week 1, the Mustangs defeated UC Davis 56-10 in Week 2. On the other hand, the Cardinals followed up their Week 1 loss to Ole Miss with a 59-13 win against Villanova.

Below, we'll break down our SMU vs. Louisville prediction and picks for Saturday’s college football game, including the spread, over/under, and key player picks on PrizePicks.

Make your SMU vs. Louisville prediction on PrizePicks now!

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#16 SMU vs. #23 Louisville Prediction, Spread, Over/Under – Saturday, September 19

SMU has certainly benefited from QB Kevin Jennings returning for a fifth season. Across the Mustangs’ first two games, Jennings has the most yards per attempt (14.8) and third-most passing TDs (8) among college QBs with 50+ dropbacks in 2026, per PFF.

SMU is in the 90th percentile in EPA/pass (0.65), via Game on Paper. The biggest issue for the Mustangs is that they’re overly reliant on converting third downs, as they are ranked in the 43rd percentile in early-down EPA/play (0.1) but 80th percentile in late-down success rate (57.1%).

Ahead of Saturday’s contest, SMU returns the second-lowest payout (6.25x) to win the ACC Championship, only behind #5 Miami (1.47x).

Transfer QB Lincoln Kienholz has also excelled through the air for Louisville, posting the second-most yards per attempt (12.5) among college QBs with at least 50 dropbacks. He's taken care of the football, tossing 4 TDs and 0 INTs in his first two starts for the Cardinals.

While Kienholz has been efficient, Louisville’s rushing attack has been even more effective, sitting in the 84th percentile in EPA/rush (0.25). That being said, Kienholz also leads the Cardinals in rushing yards (111) and rushing touchdowns (3) to begin the new season.

Louisville sits behind SMU with the third-lowest payout (10x) to win the ACC Championship despite the loss to a ranked Ole Miss squad in Week 1.

SMU vs. Louisville Spread, Over/Under – Saturday, September 19

Louisville enters Saturday’s game as a 1.5-point home favorite against SMU, returning a 1.78x payout on PrizePicks if they win outright.

Here are the full payouts for the 16 SMU vs. 23 Louisville game on PrizePicks.

Make your SMU vs. Louisville pick on the spread or over/under on PrizePicks.

Payouts show potential returns on correct PrizePicks predictions. A 2x payout returns $200 on a $100 entry. Lower multipliers reflect outcomes users are picking as more likely. Payouts are live as of writing and subject to change.

SMU vs. Louisville Prediction on Spread – 9/19/26

Here are the key game stats and trends behind our SMU vs. Louisville prediction on the spread for Saturday, September 19’s game. 

• Despite SMU’s issues on early downs, Louisville’s defense is in just the 16th percentile in early-down EPA/play (0.4) allowed.
• The Mustangs have the slight edge on defense, ranking in the 49th percentile in EPA/pass (0.1) and 63rd percentile in EPA/rush (-0.1) allowed.
• Meanwhile, the Cardinals are in the 36th percentile in EPA/pass (0.3) and 28th percentile in EPA/rush (0.2) allowed.
• Since the start of last season, SMU has a 62.5% cover rate against the spread (ATS) when facing ACC opponents, per Team Rankings.
• During that same span, Louisville has a 37.5% cover rate ATS against conference foes.
• The Mustangs have won by at least 7 points in back-to-back meetings against the Cardinals, including last year’s 38-6 victory.
• Louisville has also gone just 1-7 ATS as a home favorite since the start of 2025.

Lock in your SMU vs. Louisville prediction on PrizePicks now!

SMU vs. Louisville Picks, Player Stats for PrizePicks: 9/19/26

Here are the top SMU vs. Louisville picks to target on Saturday, September 19. Today’s college football picks for PrizePicks include WRs Jalen Cooper and Tre Richardson.

SMU WR Jalen Cooper vs. Louisville: 24.5 Longest Rec

• Of the SMU receivers with at least 30 passing-down snaps, Cooper leads the team in average depth of target (aDOT; 15.4).
• Cooper has recorded a reception of at least 42 receiving yards in both of the Mustangs’ games in 2026.
• Louisville is susceptible to big plays through the air, evidenced by them having all 4 of their passing TDs allowed this year being at least 35 yards.

Add Jalen Cooper + SMU to cover the spread to your PrizePicks lineup now.

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Louisville WR Tre Richardson vs. SMU: 64.5 Rec Yards

• Richardson has tallied 83+ receiving yards in back-to-back games to begin the new season.
• Of the 200 college wideouts with at least 10 targets, Richardson has the 21st-most yards per route run (3.9).
• Across the Cardinals’ first two games, Richardson leads the team in targets (13), receptions (11), and receiving yards (181).

Add Tre Richardson + Louisville to win to your PrizePicks lineup now.

Make SMU vs. Louisville Picks on PrizePicks

SMU and Louisville both have their sights set on making a push for the ACC title this season, and a loss for the Cardinals would give them a 1-2 record. Will the Mustangs take care of business on the road with Jennings performing well?

Don’t wait until kickoff — make your SMU vs. Louisville picks on PrizePicks now and earn real money if you’re right.

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