The Syracuse Orange take on the Clemson Tigers in Clemson, SC. Kickoff is set for 12 p.m. ET on ESPN.
Clemson is favored by -17 points on the spread with a moneyline of -800. The total is set at 55.5 points.
Here’s my Syracuse vs. Clemson predictions and college football picks for Saturday, September 20, 2025.
Syracuse vs Clemson Prediction
- Syracuse vs. Clemson Pick: Under 55.5 (Play to 54.5)
My Clemson vs. Syracuse best bet is on the under. Find the best line available on our live NCAAF odds page.
Syracuse vs Clemson Odds
| Syracuse Odds | ||
|---|---|---|
| Spread | Total | Moneyline |
+17 -110 | 55.5 -110o / -110u | +550 |
| Clemson Odds | ||
|---|---|---|
| Spread | Total | Moneyline |
-17 -110 | 55.5 -110o / -110u | -800 |
- Syracuse vs Clemson point spread: Clemson -17
- Syracuse vs Clemson over/under: 55.5 points
- Syracuse vs Clemson moneyline: Syracuse +550, Clemson -800
Syracuse vs Clemson Preview
Syracuse Orange Betting Preview: Tough Matchup for Offense
This matchup presents an intriguing clash of styles, as the Syracuse Orange run one of the fastest offenses in the nation, ranking fifth in seconds per play.
However, their volume may be negated by their inefficiency against the Clemson defense.
The Orange throw the ball nearly 59% of the time and rank fifth in pass attempts per game — although they're 91st in completion rate, 66th in yards per pass and 104th in sack rate.
They're up against a Clemson defense that's been exposed through the air, ranking 135th in opponent completion percentage and 119th in yards per pass allowed. However, it boasts an excellent defensive line, which is 41st in sack rate.
Part of those passing numbers against Clemson have also come at the hands of LSU's Grant Nussmeier and Georgia Tech's Haynes King, who are far better quarterbacks than Steve Angeli of the Orange.
If Clemson can continue to create pressure without blitzing, it could help its secondary significantly while slowing down the Orange offense.
Clemson Tigers Betting Preview: Need to Throw the Ball More
On the other side of this matchup, we have a Clemson offense that's in need of a good showing. The Tigers' upset loss against Georgia Tech last week has put their season outlook in jeopardy.
Two losses for a team that was favored to come out of the ACC isn't a good look, and it's partly due to the Tigers not playing to their strengths.
Clemson has a Heisman-caliber quarterback in Cade Klubnik, but it's only put the ball in his hands 43% of the time, which ranks 101st in the nation.
The Tigers have run the ball at the 36th-highest rate and they're only averaging 3.8 yards per carry. Meanwhile, Klubnik has been tremendous, completing 84% of his passes while ranking eighth in yards per pass.
This Clemson offense has the matchup to get right, as Syracuse ranks 116th in yards per rush allowed and 71st in yards per pass allowed.
However, the Tigers' rush-heavy approach and tempo — which ranks 127th in the country — may limit their production here.
Syracuse vs Clemson Pick, Betting Analysis
As I mentioned earlier, the Tigers possess all the necessary tools to dictate this matchup on both sides of the ball. Plus, they're in front of their home crowd.
However, from what we've seen recently, the Tigers should be able to control this game with long, methodical drives after forcing quick three-and-outs defensively.
With this game being played at their speed, we should expect them to widen the gap while time melts off the clock like a snowman on a sunny day.
Pick: Under 55.5
