Duke vs. Syracuse Prediction, Odds, Picks - September 27, 2025

Updated Sep. 27, 2025 9:04 a.m. ET

FOX Sports

The Duke Blue Devils (2-2), who have college football's ninth-ranked passing offense, take on the Syracuse Orange (3-1) and their fourth-ranked passing attack on Saturday, September 27, 2025. The Blue Devils are 4.5-point favorites. An over/under of 59.5 is set for the contest.

The Blue Devils beat the North Carolina State Wolfpack, 45-33, in their last game. The Orange's most recent contest was against the Clemson Tigers, and they won by a score of 34-21.

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Duke vs. Syracuse Game Information & Odds

When: Saturday, September 27, 2025 at 12 p.m. ET
Location: JMA Wireless Dome in Syracuse, New York
TV: ACC Network
Live Box Score on FOX Sports

Duke vs Syracuse Betting Information updated as of September 27, 2025, 8:45 a.m. ET.
Favorite	Spread (Odds)	Favorite Moneyline	Underdog Moneyline	Total	Over Moneyline	Under Moneyline
Duke	-4.5 (-110)	-190	+156	59.5	-108	-112

Duke vs. Syracuse Prediction

Pick ATS: Duke (-4.5)
Pick OU: Over (59.5)
Prediction: Duke 35, Syracuse 28

Predictions are made by the Data Skrive betting model.

Learn more about the Duke Blue Devils vs. the Syracuse Orange game on FOX Sports!

Duke vs. Syracuse Betting Insights

Per the spread and over/under, the implied score for the game is Blue Devils 32, Orange 28.
The Blue Devils have a 65.5% chance to win this contest per the moneyline's implied probability. The Orange have a 39.1% implied probability.
Duke has covered once in four matchups with a spread this season.
Syracuse has covered twice in four chances against the spread this season.

Duke vs. Syracuse: 2025 Stats Comparison

	Duke	Syracuse
Off. Points per Game (Rank)	34 (37)	38.3 (19)
Def. Points per Game (Rank)	32.3 (123)	27.5 (105)
Turnovers Allowed (Rank)	7 (117)	6 (96)
Turnovers Forced (Rank)	5 (50)	6 (27)

Duke 2025 Key Players

Name	Position	Stats
Darian Mensah	QB	1,305 YDS (67.3%) / 11 TD / 2 INT
Anderson Castle	RB	193 YDS / 3 TD / 48.3 YPG / 8.8 YPC 10 REC / 63 REC YDS / 0 REC TD / 15.8 REC YPG
Sahmir Hagans	WR	12 REC / 179 YDS / 4 TD / 44.8 YPG
Cooper Barkate	WR	17 REC / 337 YDS / 1 TD / 84.3 YPG
Vincent Anthony Jr.	DL	13 TKL / 5 TFL / 5 SACK
DaShawn Stone	DB	31 TKL / 0 TFL / 1 INT / 1 PD
Tre Freeman	LB	20 TKL / 2 TFL / 0.5 SACK / 1 INT
Caleb Weaver	DB	31 TKL / 0 TFL

Syracuse 2025 Key Players

Name	Position	Stats
Steve Angeli	QB	1,352 YDS (62.8%) / 10 TD / 2 INT -32 RUSH YDS / 1 RUSH TD / -8 RUSH YPG
Justus Ross-Simmons	WR	14 REC / 212 YDS / 5 TD / 53 YPG
Darrell Gill Jr.	WR	14 REC / 310 YDS / 3 TD / 77.5 YPG
Yasin Willis	RB	233 YDS / 4 TD / 77.7 YPG / 4.5 YPC
Braheem Long Jr.	DB	15 TKL / 2 TFL / 2 SACK / 1 INT
Demetres Samuel Jr.	DB	20 TKL / 0 TFL / 1 INT / 1 PD
Darian Chestnut	DB	21 TKL / 0 TFL
Gary Bryant III	LB	21 TKL / 0 TFL