Mathis finished 54 holes at 17-under-par 198 and is one ahead of Matt Weibring, who also shot a 68 on Saturday, but his was at a par-72 venue.
Play rotated over three courses for the first three rounds with the professionals playing with amateur partners.
The courses were the par-71 Thornblade Club, the par-72 Bright's Creek Golf Club and the par-72 Carolina Country Club. Thornblade will host the final round.
Mathis played the Thornblade Club Saturday and teed off on the 10th tee. He birdied that hole and racked up birdies at 14 and 16 to reach 17-under par.
He did not stay at that score for very long. Mathis bogeyed the 17th and 18th holes, a bad sign since he returns to Thornblade on Sunday. Those were the last mistakes for Mathis on Saturday.
His second landed in a bunker at the par-five second, but he blasted out to three feet and converted the birdie effort. Mathis hit a great putt from 25 feet at the fourth, but a little too hard. He lipped out his birdie try, but atoned for the hiccup with a two-putt birdie at the par-five fifth.
Mathis parred out for the third-round lead.
'I hit a lot of great shots, especially down the stretch and I hit good putts too and they just didn't go down,' said Mathis, who is winless on the Nationwide Tour. 'It's a fun spot to be in for sure heading into tomorrow.'
Weibring played the Bright's Creek Golf Club on Saturday. Like Mathis, he started on the second nine, and Weibring netted three birdies and a bogey in his first four holes.
He recorded birdies at one and four, but could not make another one that would've joined him with Mathis for the lead.
Peter Tomasulo (68) and Bill Lunde (67) are knotted in third place at minus-13. Marc Leishman (67) and Brendon Todd (65) share fifth at 12-under 203.
Roger Tambellini and Rich Barcelo both shot 68s on Saturday and are tied for seventh at 11-under 204. Arjun Atwal (69) and D.J. Brigman (63) share ninth at minus-10.
The 54-hole cut fell at four-under 211. Last week's winner Colt Knost and Nationwide Tour money leader Darron Stiles both missed the mark.