The Duke Blue Devils take on the Syracuse Orange in Syracuse, New York. Kickoff is set for 12 p.m. ET on ACC Network.
Duke is favored by -5 points on the spread with a moneyline of -210. The total is set at 61 points.
Here’s my Duke vs. Syracuse prediction and college football picks for Saturday, September 27, 2025.
Duke vs Syracuse Prediction, Picks
- Duke vs. Syracuse Pick: Under 60.5 (Play to 57.5)
My Syracuse vs. Duke best bet is on the under. Find the best line available on our live NCAAF odds page.
Duke vs Syracuse Odds, Spread, Lines
| Duke Odds | ||
|---|---|---|
| Spread | Total | Moneyline |
-4 -112 | 59.5 -108o / -112u | -185 |
| Syracuse Odds | ||
|---|---|---|
| Spread | Total | Moneyline |
+4 -108 | 59.5 -108o / -112u | +160 |
- Duke vs Syracuse Spread: Duke -4, Syracuse +4
- Duke vs Syracuse Over/Under: 59.5
- Duke vs Syracuse Moneyline: Duke ML -185, Syracuse ML +160
Duke vs Syracuse College Football Betting Preview
Duke Blue Devils Betting Preview
The Blue Devils kicked off their conference schedule with a bang as they defeated NC State by being a well-oiled machine offensively. Duke has shown that it can do it all behind quarterback Darian Mensah and an efficient duo in the backfield.
As for the Blue Devils' outlook against the Orange, we could see Mensah contained a bit through the air. Syracuse did a good job of holding Cade Klubnik to just 6.1 yards per pass in its upset win last week.
We've seen Mensah have success stretching the field, but that will be easier said than done against the Orange, as Syracuse ranks 53rd in yards per pass allowed and 34th in opponent completion percentage.
The Blue Devils should have plenty of success on the ground, however. Syracuse is 119th in yards per rush allowed, and the tandem of Anderson Castly and Nate Sheppard has been very effective, despite Duke rushing the ball just 40% of the time.
One thing to watch for is Duke's tempo, as it's the ninth-fastest team in terms of seconds per play.
Syracuse Orange Betting Preview
Syracuse comes into this matchup riding high off a big road upset victory against Clemson. However, it suffered a big loss towards the end of the game, as starting quarterback Steve Angeli went down with what is now a season-ending injury.
The next man up for the Orange under center is Rickie Collins. We didn't see much of what Collins could do against Clemson, as he went just 3-for-8 passing, averaging just 4.3 yards per completion.
Head coach Fran Brown says that Collins likes to sling it, so he should be a decent fit for Syracuse's offensive system. However, the 20-year-old is likely to face some growing pains, as he's inexperienced and will likely come under pressure from Duke's defensive front.
So, while he may have a good matchup on paper against a Duke defense that ranks 128th in yards per pass and 130th in opponent completion percentage, expectations should be tempered.
Duke vs Syracuse NCAAF Week 5 Pick
This total has bounced around quite a bit since opening at 59. While the moves up are certainly justified — since these are two up-tempo, pass-heavy offenses — they're each set to struggle for their own reasons.
Duke is going to have loads of success on the ground as its passing attack is contained.
Also, the Syracuse passing attack is a question mark with a new man leading the huddle.
Take the under.
Pick: Under 60.5
