Perry, who has finished in the top-10 seven times at this tournament, shot 29 on the front nine, and had no bogeys. He flirted with 59, before making par on the final two holes.
"I was looking for that magical number," Perry said. "I thought I could do it today. It was definitely in the back of my head. I was definitely trying to get it done."
Over 100 golfers shot under par, taking advantage of light winds and the soft greens left by the same rains that plagued the U.S. Open.
Former Clemson star Charles Warren and Paul Goydos shot 63s to tie for second place. They also played bogey-free rounds. Goydos had birdies on three of his final four holes, while Warren putted for birdie 16 times.
"Whoever the superintendent is has done an unbelievable job getting the golf course ready given the amount of rain you've had, Warren said. "So, I think there will be low rounds all week ... I think 59 is a possibility."
Australian Greg Chalmers had eight birdies, six over his final eight holes, and finished tied at 64 with Spencer Levin, Boo Weekley and Tag Ridings.
"Sometimes on this golf course, you get on a roll," Chalmers said.
Weekley started on the 10th hole and birdied his first six.
"I wish I could have kept the string going," he said. "We hit a lot of good putts out there and hit a lot of good shots. We just made two mistakes."
Ridings had the shot of the day, acing the par-3, 11th hole. He used a 9-iron to give the tournament its first hole-in-one since 2007, when both Craig Perks and Bo Van Pelt accomplished the feat.
"There is not a bit of wind out there," Ridings said. "The greens are firmer than anticipated but they are still soft, so they're really just perfect scoring conditions."
U.S. Open champion Lucas Glover was among nine golfers tied at 65.
Former Louisville, Ga., resident Brian Gay shot 66. Evans resident Vaughn Taylor shot 69.
But the day belonged to Perry, who has one other 61 in his career, at the 2003 Colonial.
On Thursday, he was 7-under after 10 holes, and said that's when he began the think about a sub-60 round, something that's only been accomplished three times on the PGA Tour.
"I thought, with the eagle holes coming up ... I really felt I had a shot at it," he said.