Kenny Dinkins, Mike Holloway and Ben Robinson each caught touchdown passes from Austin Brown for the Buccaneers (6-1, 3-0). Robinson also scored a 2-yard rushing TD. Solomon Brown capped the scoring with a 28-yard pick six.
Austin Brown completed 14 of 24 passes with no interceptions as Charleston Southern won in Boiling Springs for the first time since 2005.
Gardner-Webb (2-5, 1-2) gained 110 yards of total offense, its lowest output of the season. The Runnin' Bulldogs gained just 46 yards passing and 64 on the ground.
Gardner-Webb gained less than 150 yards total offense for the third time this season.
The Buccaneers victory sets up a first-place showdown in the Big South against Coastal Carolina (7-0, 2-0) next week.