LSU vs. Clemson prediction, odds, pick for college football Week 1

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It is Week 1 of the college football season, as LSU football hosts Clemson football. This will be the debut of Lane Kiffin as the head coach of the Tigers. It is time to continue the NCAA Football odds series with a Clemson-LSU prediction and pick.

Clemson comes into the season unranked in the preseason AP Poll, making it the first time since 2011 that they did not enter the season ranked. They were the top team receiving votes, while also being ranked 23rd in the coaches poll. Now, Clemson is looking for a bounce-back. In 2025, Clemson got off to a slow start. After losing their opening game to LSU, they would defeat Troy before dropping games to Georgia Tech and Syracuse. Still, the Tigers would win six of their last eight games, including the final four games of the regular season to make a bowl game. In the Pinstripe Bowl against Penn State, Clemson lost 22-10.

Meanwhile, there is plenty of hype around LSU and new coach Lane Kiffin. LSU enters the game ranked 11th in the AP Poll and 13th in the coaches poll. LSU started strong, upsetting number four Clemson and opening up 5-1. They would then win five of their last seven games before losing to Houston in the Texas Bowl. The Tigers fired Brian Kelly at the end of October, and now have a new coaching staff with much of a new roster.

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This will be the sixth time that the two schools have faced off, but just the second regular season battle, with the first coming last year. LSU has won four of the previous five meetings.

Odds provided by DraftKings

Clemson vs. LSU Odds

Clemson: +10 (-110)

LSU: -10 (-110)

Over: 50.5 (-112)

Under: 50.5 (-108)

Clemson vs. LSU Key Injuries

Clemson- S Polo Anderson (Out), LB Joseph Roberto III (Out), DT Hevin Brown-Shuler (Out), OL Adam Guthrie (Out), RB Peyton Streko (Out), DT Vic Burley (Questionable), WR T.J. Moore (Questionable), WR Bryant Wesco Jr. (Probable), WR Chris Denson (Probable)

LSU- Dae’Wuan Wright (Eligibility Concerns), Junior Tuihalamaka (Eligibility Concerns), DE Lamar Brown (Probable)

Clemson vs. LSU Betting Trends

– Clemson was just 5-8 against the spread in 2025.

– Clemson covered the spread on the road four of six times, including their only road game as an underdog in 2025.

– The under hit in eight of Clemson’s games last season.

– LSU was 4-9 against the spread in 2025.

– LSU was 2-4 against the spread as a favorite last year, and 0-3 when favored by ten or more points.

– The under hit in nine of LSU’s 13 games last year, including against Clemson to open the season.

Keys to Clemson vs. LSU matchup

Clemson will be breaking in a new quarterback with a new offensive coordinator this year. Chad Morris comes in as the Clemson offensive coordinator after not coaching in 2025. This is his second stint at Clemson, serving as an offensive analyst in 2023. His quarterback will be Christopher Vizzina, who is making just his second start of his college career. He has attempted just 105 total passes since joining Clemson in 2023. In a hostile environment, getting him settled into the game will be key. That will likely be done with quick throws to Bryant Wesco and TJ Moore, while the team has a heavy dose of Gideon Davidson out of the backfield.

Meanwhile, the defense is replacing a lot. Peter Woods and TJ Parker are both off to the NFL, putting a lot of pressure on Will Heldt. Heldt is primarily a pass rusher, having 7.5 sacks last season. Meanwhile, the secondary needs Ashton Hampton to step up and be the top corner with Avieon Terrell now in the NFL. It is a defense that has depth and brings in solid transfers, but if they let LSU get into a rhythm, it could get ugly.

For LSU, it starts with Sam Leavitt. Leavitt has faced pressure before in his career, leading Arizona State to the College Football Playoffs. Still, he played just seven games last year before going out with an injury, and has a roughly 3:1 touchdown-to-interception ratio. With the Clemson pass rush being relentless, Leavitt needs to get comfortable quickly. Further, LSU needs to be efficient on early downs. On offense, the team moved the ball well on first and second down, leading to shorter third-down conversions.

The defense was great last year on first and second downs, stuffing the Clemson run and allowing edge rushers to pin back and go after the quarterback on third down. LSU has to do that again this year, with Davidson likely getting the ball early and often. They then need to make sure to get after Vizzina and force some short fields for their offense.

Clemson vs. LSU Prediction and Pick

This game is tough to predict because of all the changes. For Clemson, it is the change at quarterback. Cade Klubnik began starting at quarterback in 2022, and now it is finally Vizzina’s turn. Clemson is 59th in the nation in returning production this year, but 94th on offense while 26th on defense. Still, the production they lost on defense was some of the best players on their team. Meanwhile, LSU is a very different-looking team. There is the question of LSU’s former professional players suiting up, but that could be cleared up before the game. Still, it is a new coaching staff and a new quarterback for the Tigers. With all the changes, the defense should be favored in this game.

Final Clemson vs. LSU Prediction and Pick: LSU -10 (-110) and Under 50.5 (-102)

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