John Merrick aced the par-3 17th and is alone in second place at 5-under-par 65.
Brandt Snedeker, Darron Stiles, Franklin Langham, Craig Lile, Erik Compton and David Hearn are knotted in third place at minus-4.
Wagner, who won this year's Louisiana Open, flew out of the gate on Thursday with a 15-foot birdie putt at the first. He hit a 6-iron to 6 feet to set up birdie at the par-3 fourth to reach 2 under par.
At the par-5 sixth, Wagner missed the putting surface with his second. He chipped to 12 feet and rolled in the birdie putt. Wagner made it two in a row thanks to a strong 7-iron approach that stopped 4 feet from the flagstick at the seventh.
He made the turn at 4 under par, but promptly gave one back. Wagner's drive at the 10th found the trees and he could not convert a 6-footer for par. He reclaimed the lost stroke with a 12-footer at the par-5 11th.
Wagner's second at the par-4 14th found a bunker, but he holed out from the trap for his sixth birdie. He took sole possession of the lead with a long birdie putt at the 16th.
'I made a lot of putts, got a lot of good breaks and just capitalized on every one of them,' said Wagner, who only needed 24 putts to make it around the Hardscrabble course on Thursday.
Wagner is third on the Nationwide Tour money list thanks to the win in Louisiana. That puts him in good shape to earn his PGA TOUR card, but Wagner is not resting yet.
'Right now, there's almost no pressure because I'm so close,' said Wagner. 'But, I'm still not there. A good week here can solidify that. It was probably one of the best rounds I've ever had out here.'
Merrick collected three birdies over his first nine holes, then bogeyed the 10th. He recorded back-to-back birdies from the 12th, but dropped another shot at the par-3 15th.
He fell down to 3 under par until the ace at the 204-yard, par-3 17th. That vaulted him into second place by himself.
Scott Dunlap, Scott Parel, Josh Broadaway, Scott Gutschewski and Dicky Pride share ninth place after opening rounds of 3-under-par 67.