Bo Van Pelt carded a 6-under-par 65 and is alone in second place at minus-6.
Last week, Tiger Woods and Vijay Singh both missed the cut at the Funai Classic at Disney World and things remained bad for Singh, who won this title last year.
Singh, the No. 2 player in the world, never overcame a 3-over-par 74 on Thursday. He managed an even-par 71 on Friday and missed the cut by a shot as he finished at 3-over-par 145.
The last time Singh missed back-to-back cuts on the PGA Tour was 2001. In the fall of that year, Singh failed to make the weekend at the Canadian Open, then the following week at the Pennsylvania Classic.
On Friday, Lowery broke into red figures with an 18-foot birdie putt at the par-4 third. He parred his next four, but missed a 6-footer to save par at the 235-yard, par-3 eighth.
The 45-year-old caught fire on the back nine. He hit a 7-iron to 32 feet at the 10th and ran home the long birdie putt. Lowery collected back-to-back birdies with a short one at the par-5 11th, then made it three in a row with a 15-footer at No. 12.
Lowery was not done making birdies. He knocked his second on the green from 280 yards out at the par-5 14th, then two-putted from 35 feet for his fourth birdie in five holes.
Lowery was 7 under par for the championship, but had one more birdie left in him. He hit a 5-iron with his second shot at the par-4 16th and rolled in the 25-footer for birdie.
'It's a great golf course. It's very tough,' acknowledged Lowery. 'If you're in the fairway, you can shoot some good scores. I am playing well. You get a few breaks to be leading. Hopefully, you get a few on the weekend.'
Lowery has enjoyed an interesting 2005 season. He missed the first eight cuts of the year, then 11 out of 12. Lowery sent in his application for Qualifying School, but a tie for eighth in Vegas two weeks ago earned him $112,000 and put him comfortably in the top-125.
He entered this week with six consecutive cuts made, including two eighth-place ties. Lowery sits 109th on the money list so now it may be time to add his third PGA Tour victory and first since the 2000 Southern Farm Bureau Classic.
'It is tough when you are not playing well, you don't think you'll ever play well again,' admitted Lowery. 'I don't think I ever missed that many cuts in a row. I had to start practicing harder and recommit myself to improving. It took a long time to get going.'
Van Pelt, 57th on the PGA Tour's money list, was flawless on Friday. He tallied six birdies, three on each side, as he is the hunt for his first PGA Tour title.
Two-time U.S. Open winner Retief Goosen (71), Justin Rose (68), Tim Herron (67), American Ryder Cup captain Tom Lehman (71) and Charles Howell III (71) are knotted in seventh place at minus-4.
This is a big week for Howell in particular. It is the final full-field event and Howell sits 30th on the money list, which would be the last spot in next week's Tour Championship.
Rocco Mediate is 125th on the list, the last spot for a tour card next year. He shot an even-par 71 on Friday and is part of a group tied for 12th at 3-under-par 139. Also in that group is first-round leader Jeff Brehaut, who only managed a 3-over 74 in the second round.