Flesch, who began the day one shot off the lead, was at 13-under 131, one stroke ahead of first-round co-leader Jeff Gove (67) and Brendon de Jonge, who carded his second straight 66. Charles Warren (65) was alone in fourth at 11 under.
Rookie Matt Hendrix, a former star at Clemson, had his second straight 67 and was tied for fifth at 10 under with Chris Stroud (65) and Charley Hoffman.
Jeff Maggert (64) was another shot back, tied at 135 with Jeff Overton (65), Mathew Goggin (69), Briny Baird (66), Bill Haas (66) and three others.
Joey Sindelar, from nearby Horseheads and a two-time winner of the B.C. Open, and Robert Gamez each shot a second straight 68 and were tied at 8 under with John Senden (70), Tag Ridings (69), Johnson Wagner (67), John Rollins (69), and four others.
Chad Campbell, who had a share of the first-round lead, had an even-par 72 to remain at 7 under.
With conditions again ideal on a hazy, humid day with temperatures in the 80s and a slight breeze, Flesch started at No. 10 and quickly built on his opening 66, making four birdies and an eagle for a record 30 on the back side of the forgiving 7,482-yard Atunyote Gold Club course, with its wide fairways and soft, smooth-rolling greens.
Flesch hit a 3-wood to within 14 feet at the 562-yard, par-5 12th hole and made eagle to reach 9 under, birdied the next two holes and sank a 15-foot birdie putt at No. 18 to tie de Jonge for the lead at 12 under.
Flesch, who started the tournament with six birdies on his first eight holes on the front side, took sole possession of the lead with a 17-foot birdie putt at the par-4 second hole.
'If I get that putting going, that's my strength,' said Flesch, who has hit 34 of 36 greens in regulation. 'It really makes the game a lot easier.'
The lone blemish was a three-putt bogey from 35 feet on his final hole, which ified a birdie putt at No. 8.
If not for No. 9, Flesch would have had a bigger lead. He made double bogey there on Thursday.
'I've just played it poorly,' he said. 'My putter let me down. It's all right. I made so many putts today.'
De Jonge, a 27-year-old native of Zimbabwe and a former star at Virginia Tech, began to move up the leaderboard with an eagle at the 548-yard, par-5 fifth hole, hitting 3-wood to the right fringe and sinking a 26-foot putt. That made up for a bogey at No. 4, and he made four birdies on the back side to take the lead until Flesch came through a couple of hours later.
'The position that I've put myself in coming into these last seven events, I have to play well,' said de Jonge, who has made only seven cuts in 20 events and is far down the money list. 'You know, I've pretty much got nothing to lose. It's almost, in essence, a seven-week tour school for me, so I have to play well.'
Gove, who started at the 10th hole, finished with five birdies on a bogey-free round, tying de Jonge with a 3-foot birdie putt at the par-4 eighth hole.
'Most of my play today I was staying in the moment, playing well, staying positive and trying to stay aggressive because the scores are low,' said Gove, who birdied two of his first three holes and then reeled off eight straight pars. 'You've got to stay patient. You have to just wait for your next little run.'
Turning Stone, with a purse of $6 million, kicks off a new seven-tournament run called the PGA Fall Series that will decide the final money leaders list. The top 125 players retain fully exempt status to play on Tour in 2008, and the Fall Series determines Nos. 31 through 125.
After two rounds, a shakeup near the bubble was at hand.
Steve Allan (69), who began the tournament at No. 125 in earnings, improved on his first round by seven shots but failed to make the cut, as did Joe Durant (No. 121) Bob Heintz (No. 122), Doug LaBelle II (No. 124), John Merrick (No. 127), Frank Lickliter II (No. 130), Jason Dufner (No. 132), Ryan Palmer (No. 136), and Tripp Isenhour (No. 137).
Four players near the cutoff -- Ryan Armour (No. 123), Haas (No. 126), Alex Cejka (No. 128), and Wagner (No. 131) -- will play on the weekend. And Wagner, Haas, and Cejka were in position for a decent payday come Sunday.