Zach Johnson, who won the BellSouth Classic in April, carded a 68 to finish alone in fourth place at 6-under-par 204.
Campbell fired a 61 for the second time in his career on the PGA Tour. He won last year's Tour Championship after a 61 in the third round and the Texan made strides on Saturday to grace the winner's circle again.
'I feel like I've been hitting the ball pretty well,' said Campbell, who also won this year's Bay Hill Invitational. 'When you're making putts, it makes the game a lot easier.'
Campbell rocketed out of the gate at Colonial Country Club with an eagle at the par-5 first and added back-to-back birdies from the second to keep the run going.
He stumbled to a bogey at the par-3 third, but countered with a birdie at the fifth. Campbell then birdied the seventh but gave another shot back with a bogey at the very next hole.
The 29-year-old caught fire on the inward half and converted a 6-foot birdie putt at the par-5 11th. He played his approach to 30 feet and drained the putt for a birdie at the 12th and knocked his tee shot inside 12 feet at the par-3 13th.
Campbell converted the birdie try to make it three in a row and rolled in a 15-foot putt for a birdie at the 15th to reach 7 under. Campbell then dropped his second shot within 7 feet of the cup at the par-4 17th and birdied the hole to equal the course record shared by five others.
'I don't know how many course records I've got,' said Campbell. 'I think I've still got it in my hometown of Andrews. I'm not totally sure of that.'
Gay also had an impressive start and tallied five birdies over his first nine holes to grab a share of the lead at minus-8.
The 32-year-old, who was born if Fort Worth, hit his approach to 14 feet at the 10th for the first of three consecutive birdies to break free of his competitors at 11 under.
Gay struggled down the stretch, however, and missed the green at the 14th en route to a bogey. He then bogeyed the 16th and missed the fairway on his way to a bogey at the last to fall back into a share of the lead.
'Things are going great, obviously,' said Gay, who shot a 65 on Saturday. 'I'm hitting it nice. The putter got hot. Hopefully I can go out and do the same things starting out tomorrow, too.'
Flesch's round wasn't quite as flashy as the other co-leaders', but he did enough to remain well in contention.
The left-hander birdied two of his first three holes and ran off a string of pars before finding trouble with a bogey at the 12th. Flesch responded at the very next hole with a 20-footer for birdie and added a birdie at the par-3 16th to join Campbell and Gay in the lead after a round of 67.
Justin Leonard, who shot a 61 in the final round of this event last year, held a share of the lead heading into the weekend but struggled to a round of 72. Leonard was joined by Robert Gamez, Frank Lickliter, Brian Bateman, Mark Brooks, Brett Quigley and Tim Petrovic at 4-under-par 206.
Masters champion Phil Mickelson was one shot further back along with Scott Verplank, Bob Tway, Skip Kendall, Chris Riley, Stewart Cink, Stephen Ames, Tim Clark, Fred Funk and Lee Janzen at 3-under-par 207.
Defending champion Kenny Perry, who also fired a 61 at this event last year, followed in a group at 2-under-par 208. Overnight co-leader J.L. Lewis managed a round of 75 to fall back to 1-under-par 209.