Louisville vs. Clemson prediction: College football best bets, picks, odds

The Tigers can’t lose. 

Since dropping that tough season-opening matchup against Georgia, Clemson has racked up six consecutive victories, sitting atop the ACC standings with a 5-0 conference record. 

Cade Klubnik has thrown 20 touchdowns during the stretch.

The Tigers have scored 40-plus points in five separate games.

They’ve out-scored their opponents 291-127. 

But I think they’re overvalued entering Saturday’s matchup with a sneaky-tough Louisville squad. 

Louisville vs. Clemson odds

Louisville vs. Clemson prediction

(7:30 p.m. ET, ESPN)

Sure, the Tigers have looked dominant. 

They’ve also played nobody.

The past six wins have come against App State, NC State, Stanford, Florida State, Wake Forest and Virginia, six squads with a combined 13-29 record against FBS opponents. 

They also benefitted from a +10 turnover differential across the six victories, perhaps inflating some of those blowouts. 

Meanwhile, Louisville has battled 8-0 Miami (FL), 7-1 Notre Dame and 7-1 SMU in the past month.

The Cardinals have lost three of their past five, but those were three one-possession losses to three teams in the College Football Playoff hunt. 

I don’t trust Louisville’s defense, but Tyler Shough is dealing, leading an offense that ranks eighth nationally in EPA per Dropback.

And top running back Isaac Brown has amassed 650 rushing yards and six scores at nearly eight yards per carry. 

If the Cardinals’ offense can score a combined 96 points against the Hurricanes, Irish and Mustangs, they can score against a Tigers stop unit that ranks 76th nationally in EPA per Play allowed.

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Louisville vs. Clemson pick

The schematic, on-the-field matchup isn’t great, but I expect Clemson to struggle against a clear step-up in competition.

Meanwhile, Louisville has proven it can keep pace with anybody. 

10 points are too many for the Cardinals to be catching. 

Pick: Louisville +10.5 (-110, bet365)

Why Trust New York Post Betting

Tanner McGrath has been a professional sports handicapper since 2018. Specializing in college sports and baseball, he’s a diehard fan of the Vermont Catamounts, the Miami Marlins and any home underdog. He found himself on the wrong side of the Miami Miracle in 2018, but made up for it four years later by hitting a 40/1 long shot on Sandy Alcantara to win the NL Cy Young.