Syracuse Orange vs SMU Mustangs Prediction, Odds and Picks for Saturday, 10/04/25

The Syracuse Orange take on the SMU Mustangs in what is an interesting spot for both squads. SMU is coming off a bye week after falling to rival TCU while the Orange were embarrassed 38-3 in a loss against Duke, their first full game without QB Steve Angeli after his Achilles injury. Despite the optics of last week’s loss for Syracuse, this feels like a bit of a market overreaction. SMU is 0-4 against the spread this season and ranks 122nd in total defense among FBS teams. 

This is an ideal spot for QB Rickie Collins to get his feet under him in his second career start. Before Angeli’s injury, the Orange had a top-10 passing offense and the scheme should fare well against the Mustangs defense that ranks 88th in defensive efficiency against the pass and 99th in EPA/dropback. With a 17.5-point spread, I see value on the Orange to at least avoid a blowout against an SMU squad with an incredibly suspect defense. I’ll take Syracuse to cover.

Syracuse vs SMU prediction: Syracuse +17.5 (-110) available at time of publishing. Playable at that number or better.