South Carolina vs. Missouri Prediction, Odds and Key Players to Watch for College Football Week 4

Betting odds, pick and prediction for the South Carolina-Missouri matchup in Week 4 of the college football season.

Missouri Tigers quarterback Beau Pribula is looking to lead his team to a 4-0 start. / Denny Medley-Imagn Images

The Missouri Tigers are 3-0 to start the 2025 season and currently ranked in the top-25 heading into an SEC clash with the South Carolina Gamecocks in Week 4. 

South Carolina is in trouble this season, as it lost badly to Vanderbilt in Week 3 and may have lost quarterback LaNorris Sellers for an extended period in the process. Without Sellers finishing the Week 3 loss, South Carolina scored just seven points against Vandy.

Now, it is set as a 13.5-point underdog against the Tigers in Week 4, and Missouri’s offense has been a juggernaut to start the season, averaging 587 total yards per game. 

Here’s a look at the latest odds, a key player to watch and my prediction for this Week 4 battle. 

South Carolina vs. Missouri Odds, Spread and Total

Odds via DraftKings Sportsbook

Spread

• South Carolina +13.5 (-110)
• Missouri -13.5 (-110)

Moneyline

• South Carolina: +400
• Missouri: -535

Total

• 46.5 (Over -110/Under -110)

South Carolina vs. Missouri How to Watch

• Date: Saturday, Sept. 20
• Time: 7:00 p.m. EST
• Venue: Memorial Stadium
• How to Watch (TV): ESPN
• South Carolina record: 2-1
• Missouri record: 3-0

South Carolina vs. Missouri Key Player to Watch

Beau Pribula, Quarterback, Missouri

Missouri quarterback Beau Pribula is off to a strong start in the 2025 season, throwing seven touchdowns to just one pick while completing an SEC-best 76.4 percent of his passes.

The Tigers have put up big offensive games to start the season, scoring 42 or more points in every matchup. Things will be a little tougher against a South Carolina defense allowing just under 310 total yards per game, but Pribula is showing that he’s a starting-caliber quarterback in the SEC after sitting behind Drew Allar at Penn State. 

South Carolina vs. Missouri Prediction and Pick

South Carolina’s offensive struggles finally came to light in Week 3 against Vandebilt, as the team mustered just seven points and lost quarterback LaNorris Sellers to an injury in the process.

If Sellers misses this game, the Gamecocks are going to have a hard time keeping up against a Missouri team that has won by some wide margins so far in 2025.

Still, I think the best bet in this game is the UNDER – especially if Sellers doesn’t play.

South Carolina allowed just 11 points to Virginia Tech in Week 1, but the team has really struggled to score in bunches outside of a cupcake matchup against SC State. 

Meanwhile, Missouri has given up six, 31 and 10 points in its three games. It did allow 31 to a Kansas team led by veteran quarterback Jalon Daniels, but I don’t see that being the case if South Carolina doesn’t have Sellers on Saturday.

I’m betting on a low-scoring affair in this SEC matchup, as Missouri is averaging just 200.7 total yards of offense per game in 2025. 

Pick: UNDER 46.5 (-110 at DraftKings)

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Odds refresh periodically and are subject to change.

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