Alex Cejka (69) and John E. Morgan (68) share second place at 15-under-par 201. John Maginnes fired a 5-under 67 to grab a share of fourth place alongside David Gossett and Brett Quigley at 14-under-par 202.
Most of the field finished their second round earlier Saturday after five hours worth of weather delays on Friday. Action was also delayed Saturday at the outset due to fog.
Lowery, who tied Joey Sindelar's 36-hole scoring mark of 16-under-par 128, also matched the 54-hole scoring record of 196 set by Calvin Peete in 1982. Lowery will try to match Sindelar as the only wire-to-wire winners of this event.
The University of Alabama alum started slowly in the third round. He opened with seven consecutive pars before two-putting for birdie at the par-5 eighth.
'After back-to-back 64s, I just tried to stay patient on the front nine,' said Lowery. 'I made a good up-and-down on No. 9 to keep my momentum.'
Around the turn, Lowery began to heat up. He sank a six-foot birdie putt at the 11th and converted another birdie on 12 to make it two straight. He could not sustain that momentum, however, as he bogeyed the par-4 13th.
Lowery again sank back-to-back birdies from the 15th to climb to 20-under and extend his lead to five strokes.
'I'm going to come out very focused tomorrow and just play my game,' said Lowery, whose last win came at the 2000 Southern Farm Bureau Classic. 'I've been in this position before.'
Cejka began the third round four strokes behind Lowery and would have stayed in that position if not for a late bogey. He birdied the second before running off nine straight pars.
The 32-year-old matched Lowery's hot streak with his own birdies on 12 and 13. He climbed to 16-under with a birdie at No. 16. However, he bogeyed the final hole to drop five behind the leader.
'I am pleased with how I played,' Cejka said. 'I didn't putt well early on. I was hitting some good shots, but couldn't make a putt. I am five shots back, but tomorrow is the last day and anything could happen.'
Morgan also climbed to minus-16, but could not stay there. He ran off three straight birdies from the par-5 third, but the run was halted by a bogey at No. 6.
He again sank three birdies in a row from the eighth to get to minus-16. However, Morgan stumbled to a double-bogey at the 15th to drop off the pace. He did manage to birdie the final hole to get back within five shots.
Brian Henninger and Rod Pampling share seventh place at 13-under-par 203. Champions Tour player Craig Stadler heads a group one stroke further back at minus-12. Also in that group is Stephen Allan, Joel Edwards, David Frost and Robert Gamez.
Chris Downes, a Monday qualifier who posted the round of the afternoon at 8-under 64, and defending champion Spike McRoy are tied at 11-under-par 205. Five other players - Guy Boros, Glen Day, Carlos Franco, Per-Ulrik Johansson and Hank Kuehne - are also tied at minus-11.