Duke Blue Devils vs Syracuse Orange Prediction, Odds and Picks for Saturday, 09/27/25

The Duke Blue Devils picked up a 45-33 victory at home against previously unbeaten NC State last Saturday at Wallace Wade Stadium, and it earned its first cover of the season in four tries. Duke has been a little tough to figure out, as it was dusted by Illinois, 45-19, in the first game against an FBS opponent, and the Blue Devils lost 34-27 on the road against Tulane in its first road test on Sept. 13. Defense has been an issue for the Blue Devils, as they’ve allowed at least 33 points in all three games against FBS opponents this season, but they’ve also scored at least 27 points in three of four games.

For Syracuse, it lost 45-26 to Tennessee in the opener on a neutral field. The Orange have rallied for three straight wins over UConn, Colgate and Clemson, with the latter being the most shocking. After wins over the Huskies and Raiders, we still weren’t sure what to make of Syracuse. But, it went down to Death Valley and topped the Tigers 34-21 as a 17.5-point underdog. Former QB Steve Angeli is making the most of his chance to start, and this offense has been rolling. It’s a bit surprising that Duke is favored here, so if you’re a Same-Game Parlay (SGP) player, consider the Orange plus the points, too. But, the top play is going high on the total, as both of these teams can score, and Duke hemorrhages points and yardage.

Over 60 (-110) at time of publishing. Playable to 61.