Mauk was taken off the field on a stretcher after being injured trying to recover Bryant's fumble in the third quarter. He was on his stomach when medical personnel arrived. After several minutes, Mauk got into a sitting position and was loaded onto a stretcher.
A school official said Mauk was taken to a local hospital with an upper arm injury. No further information was provided.
Redshirt freshman Riley Skinner took over at quarterback and two plays later Wake took a 13-10 lead on Sam Swank's 40-yard field goal.
Syracuse quarterback Perry Patterson was just 5 of 18 for 45 yards and was sacked three times, and Curtis Brinkley was the Orange's leading rusher with 49 yards on eight carries as Syracuse (0-1) lost its 10th consecutive game.
Mauk was 14 of 21 for 105 yards, one touchdown and one interception. He led Wake on a 96-yard touchdown drive in the first quarter, capped by his 14-yard touchdown pass to Willie Idlette that gave Wake a 7-0 lead.
Syracuse, which ranked 115th of out 117 Division I-A teams in total offense last season, responded with an 86-yard touchdown drive. Patterson's 20-yard pass to Rice Moss with 2:59 left in the first quarter made it 7-7.
The teams exchanged field goals in the second quarter as Andrews, who rushed for 254 yards in Wake's season opener last year while replacing last year's ACC player of the year Chris Barclay, eclipsed 100 yards on a 15-yard run in the final minute of the half.
Andrews was limited in the second half with cramps and forced him into the locker room for a portion of the third quarter.
Mauk, who came into the season as the clear No. 1 quarterback after sharing the duties with senior Cory Randolph last season, threw an interception in the third quarter. Syracuse lost a fumble to Wake Forest on the next play.
The Demon Deacons, who began their first drive from their own 4-yard line, went to Andrews on their first three plays from scrimmage. The junior gained 2, 7 and 7 yards and later bounced to the right for an 18-yard gain before Mauk's TD pass.
Syracuse, coming off a 1-10 season, failed to convert their first seven third-down chances and generated only 136 yards of offense and 11 first downs in the first meeting between the schools.