The 45-year-old Pampling opened with consecutive 9-under 63s at The Reserve at Lake Keowee and Green Valley Country Club and shot a 69 on Saturday at Thornblade Club - also the site of the final round.
''I don't care where you're playing, to shoot 25 under and win only by two, that's a tribute to the quality of players out here,'' Pampling said. ''There are so many great players out here. It feels fantastic. It's tough to win anywhere these days.''
Pampling earned $121,500 for his first career victory on the tour. The two-time PGA Tour winner was two strokes off the tournament record of 27-under 259 set by Mark Anderson in 2013.
He jumped from 72nd to eighth on the money list with $147,460, putting him in position to earn a PGA Tour card for next season.
''Once you're on the PGA Tour it's pretty easy to stay out there, but getting back is extremely difficult,'' Pampling said. ''You've got to dig deep. This one is pretty special.''
Kelly Kraft was second after a 66.
Roland Thatcher shot a course-record 11-under 60 to finish third at 21 under. He had an eagle and nine birdies on the first 16 holes, then closed with two pars to miss a chance for a 59.
''I had a feeling like this was out there this morning,'' Thatcher said. ''It was the best warm up session I had since I could remember. I told my caddie it was going to either 60 or 80, and I happened to be right.''