LSU vs. Clemson: Prediction, Odds, Betting Preview

Who says there aren’t interesting Week 1 college football games? 

LSU and Clemson are playing a battle of the Death Valleys that will make the short list of the best and most important games of the 2025 Labor Day weekend. Naturally, BetMGM has loads of college football odds tied to this game.

That’s not just the typical six-pack markets, either. Expect the winner of this team to get a clear bump in the college football national championship odds markets. (I also have Clemson making the playoff in my CFP predictions.)

Maybe most importantly, this game is a quarterback duel with huge implications in the Heisman Trophy odds market, since both LSU’s Garrett Nussmeier and Clemson’s Cade Klubnik start the season as two of the top three names in the table.

Hypothetically, the winner could jump Arch Manning and become the favorite … depending on what happens in the Texas vs. Ohio State game.

And if all that isn’t enough, I do like a particular side in this game. So there is a lot going on here. 

LSU vs. Clemson Odds

• Point Spread: Clemson -3.5
• Moneyline: Clemson -185  |  LSU +150
• Over/Under: 57.5

LSU vs. Clemson Preview

I really respect what Clemson and LSU do in the scheduling department. In an era where it’s easy for powerful programs to coast against bad teams and reap the December rewards of an inflated record, both groups of Tigers consistently play tough nonconference opponents.

Since 2021, LSU has played USC, Florida State (twice), and UCLA. Clemson has played Georgia twice and Notre Dame twice since 2020, plus its annual game against rival South Carolina.

On Saturday, much will be made of Clemson’s 1-3 record against LSU. But the last game was played in the 2019 playoff, when LSU dismantled everyone and rolled to the national championship behind Joe Burrow and a stacked roster. The other three games were before that. So I’m not sure how much bearing the all-time history has on this week. 

Much more relevant: Clemson’s 2-8 ATS streak vs the SEC, or its 2-6 ATS streak in openers against P4 opponents. 

But LSU is no beauty in this department, either. LSU has actually lost its last five opening games outright, which is a tough referendum on head coach Brian Kelly. (Overall, I remain a Kelly defender.)

The over is a popular target in this game at BetMGM thanks to a potential sharp handle split. About 54% of the total tickets were on the under, as of Monday, but 63% of the overall handle was on the over. Given the two quarterbacks and a modest college total of 57.5, this makes some sense to me.

But I feel more comfortable with a prediction on the side in this game. I am extremely high on Clemson football odds this year, with all it brings back on top of Klubnik. They’ll have an excellent home-field advantage in this game, and I believe they’ll go on to contend for the national title.

On top of the winless season opener streak, LSU is 1-3 ATS in road games against ranked opponents under Brian Kelly. (The lone cover was at No. 21 Missouri in 2023.)

LSU vs. Clemson Prediction

I am predicting a Clemson win and cover against LSU on Saturday.

I don’t want to make it sound like I’m down on LSU this year because I think they’ll be good. But I think Clemson can be great, and that should be the difference in this game. 

LSU vs. Clemson Prediction: Clemson -3.5