Mathis, who led after the second and third rounds, cruised to a 3-under 68 to finish the tournament at 20-under-par 266.
'Gosh, I just wanted to play well so bad,' stated an emotional Mathis. 'It's awesome.'
It was his first win on tour and came a two weeks after he closed with a 74 to end in sixth at the South Georgia Classic.
'I think I just got so ahead of myself early in the round and I wanted to put pressure on the leader. I think I just got fast and bogeyed a couple holes early,' admitted Mathis. 'Man, I'm just so thankful.'
Roger Tambellini fired a 6-under 65 Sunday to end alone in second place at 17-under-par 269. Matt Weibring, who was also searching for his first tour win, closed with an even-par 71 to take third at minus-16.
After play rotated over three courses for the first three rounds, the par-71 Thornblade Club hosted the final round. The other two courses were the par-72 Bright's Creek Golf Club and the par-72 Carolina Country Club.
Mathis, who played Thornblade on Saturday as well, got his round going with a birdie on the second. After a par on the third, Mathis dropped in back-to-back birdie efforts from the fourth to get to 20-under.
The 34-year-old stumbled to a bogey on the par-4 seventh, but he still led by three. Mathis cruised to seven straight pars as no one got closer than two shots the whole time.
At the back-to-back par-5s, Nos. 15 and 16, Mathis collected a pair of birdies to push his lead to four strokes. He was unable to get up and down from a bunker at the last, but a bogey was more than enough for the win.
The win moves Mathis to fourth on the money list and nearly guarantees his PGA TOUR card for next year.
'Absolutely, top 25 is what you are looking for,' Mathis said. 'To think of all the things I've come through to get to this point, gosh it's just awesome.'
Tambellini carded four birdies in his first seven holes to jump to 15-under. However, he could only birdie two of his last 11 holes to end three back.
Weibring, who tied for fifth last week, traded a bogey for a birdie from the first. He faltered to a double-bogey at the ninth to make the turn at minus-13. Weibring ran off three birdies in a four-hole stretch from the 13th to get back to 16-under.
Bill Lunde took fourth at 15-under-par 271 after a final-round 69. Peter Tomasulo was two shots further back at minus-13.
Marc Leishman and Brendon Todd shared sixth at 12-under-par 274, while Arjun Atwal and Kim Felton were one further back at minus-11.