The Orange were led by fourth year head coach Doug Marrone and played their home games at the Carrier Dome.

They were invited to the Pinstripe Bowl where they defeated long-time rival West Virginia, whom they did not play in the regular season due to the Mountaineers' move to the Big 12 Conference.

Key offensive players such as Alec Lemon, Marcus Sales, Jerome Smith, and Prince-Tyson Gulley are also returning.

On defense, key players returning include Shamarko Thomas, Marquis Spruill, and Deon Goggins.

The program lost a number of significant contributors in the 2011 campaign, including tight end Nick Provo and defensive end Chandler Jones, and such losses left a number of questions regarding how a relatively young defense would be able to mature without many experienced players.

A dominating 4th quarter performance by USC quarterback Matt Barkley proved to be too much, however, as the Trojans dealt Syracuse their second loss with a final score of 42–29.

This victory snapped an eight-game FBS losing streak, and was the Orange's first win over Pitt since a double-overtime affair in 2004.

1st quarter scoring: RUT: Jawan Jamison 1 Yd Run (Nick Borgese Kick) 2nd quarter scoring: SYR: Adonis Ameen-Moore 3 Yd Run (Ross Krautman Kick) 3rd quarter scoring: RUT: Duron Harmon 75 Yd Return Of Blocked Field Goal (Nick Borgese Kick); RUT: Nick Borgese 25 Yd FG 4th quarter scoring: SYR: Christopher Clark 40 Yd Pass From Ryan Nassib (Ryan Nassib Pass To Marcus Sales For Two-Point Conversion) The Connecticut Huskies took on the Orange in former Syracuse head coach Paul Pasqualoni's first return to the Carrier Dome since he was fired at the end of 2004 season.

Daniels (Maikon Bonani Kick); SYR: Marcus Sales 19 Yd Pass From Ryan Nassib (Ross Krautman Kick); SFL: Maikon Bonani 47 Yd; SYR: Alec Lemon 1 Yd Pass From Ryan Nassib (Two-Point Pass Conversion Failed) Looking to go above .500 for the first time all season, the Orange entered Cincinnati and lost a sloppy contest that featured five total turnovers.

Despite doubling the Bearcats' total yardage and 286 passing yards from Ryan Nassib, Syracuse fell to 4–5 on the season.

Behind a dominating offensive performance from quarterback Ryan Nassib and running back Jerome Smith, Syracuse put up 524 total yards as they won by a score of 45–26.

Syracuse entered the game riding a two-game winning streak over the Mountaineers, including a 49–23 blowout the previous season.