Anthony Painter also shot a 64 in the second round and is alone in second place at 7-under-par 133. Chris Couch (66), Jason Schultz (66), John Morse (68), Brian Kortan (67) and first-round co-leader Ben Bates (71) are knotted in third at minus-5.
Villegas wasted little time in breaking into red numbers with a 10-foot birdie putt at the first. He collected back-to-back birdies at three and four, from 20 and 25 feet, respectively.
He reached the green in two at the par-5 sixth, but three-putted from 25 feet for par. Villegas tapped in a 2-footer for birdie at the ninth to make the turn in 31.
Villegas missed the green with his 5-iron second shot at the par-5 11th. He got up and down for birdie, then added another short birdie putt at the 13th.
He parred his remaining holes to grab first.
'I'm going to keep doing what I'm doing,' said Villegas. 'I have to stay patient, hang in there, make a few putts and see what happens. Hopefully, I can finish strong on the weekend.'
Villegas tied for second earlier this year at the BellSouth Panama Championship. He has missed the cut in his last two starts, but Villegas thinks he might be ready to break into the winner's circle.
'Leading in Panama showed me I could compete out here,' said Villegas. 'This game is so competitive. It's tough to say you're going to go out and win when you don't even have your card. Whatever it takes.'
Aaron Barber (71), Tom Scherrer (71), Troy Matteson (71), Scott Weatherly (68), Dave Christensen (68) and David Morland IV (69) are knotted in eighth place at 4-under-par 136.
Kevin Durkin shared the opening-round lead with Bates, but struggled to a five-over 75 on Friday. He is part of a group tied for 23rd place at 1-under-par 139.
The 36-hole cut came at 1-over-par 141 and 65 players made it to the weekend.