Flesch, who birdied the last two holes to finish at 15-under 201, also had two bogeys in winds that gusted up to 30 mph and swirled through towering pines on the 7,472-yard Montreux Golf & Country Club on the eastern slope of the Sierra Nevada.
He opened the $3 million tournament with a 9-under 63 in search of his third career victory on the PGA TOUR.
'Anytime you can birdie the last two holes I think you'll be hard to beat,' said Flesch, whose five-stroke lead is the biggest through 54 holes at any PGA event this year. The biggest previous lead was Tiger Woods' four-stroke advantage at the World Golf Championships-CA Championship.
'It was a lot like playing yesterday afternoon to be honest with you,' said Flesch, a 40-year-old left-hander from Kentucky who has earned more than $13 million in 11 years on tour. 'I think today I was a little more conservative because of the wind. I picked my spots out there where I tried to be aggressive.'
PGA TOUR rookie John Merrick had six birdies and two bogeys in a round of 68 to get to 10-under 206 and a tie for second with Australian Steve Allan (69) and Todd Fischer (69), who has a home on the golf course.
Charles Warren, who shot a 63 on Friday and opened the day at 10-under, double bogeyed the second hole en route to a 73 to fall back to 9-under 207.
Kevin Stadler (67), Steve Elkington (69) and Jose Conceres (72) were next at 9-under 208. Jeff Maggert (67) and Shaun Micheel (71) were in a group another stroke back at 8-under par.
Merrick, a former all-Pac 10 golfer at UCLA who is 141st on the money list with $362,000, had three top-25 finishes in the middle of the season but has missed the cut five of his last seven outings.
'It's nice to see your name on the leaderboard. Mine hasn't been up there much this year,' he said. 'I've been trying a little bit too hard I think. This week I've been trying not to put too much pressure on myself.'
Merrick said the winds added to the difficulty of deciding which clubs to use given the nearly 10 percent farther the ball travels at the high elevation.
'I hit 6-iron into No. 9 today and it's a 615-yard, par 5,' Merrick said. 'The winds all over the place. ... One second it's downwind. The next second it's into the wind.'
'There's an element of luck out there because the way the wind swirls it's impossible to pick (clubs) sometimes,' he said. 'You can be penalized for some shots that aren't bad shots.'
Fischer, who missed the cut in his only two PGA outings this year at the AT&T Pebble Beach and the U.S. Open, is playing on a sponsor's exemption. He said he treats this tournament as his 'No. 1 major.'
'It was the only one I was looking forward to all year because I knew I was in it,' he said.
Flesch said his wedge play has kept him out of trouble all week. He missed the par-3 second hole long Saturday but chipped up to 4 feet and made the putt to save par. He missed a 5-foot birdie putt on the next hole, then made one from 9 feet for a birdie on the par-4 fifth.
Flesch gave the stroke back on the 220-yard seventh when he hit 3 feet past the green into the rough, chipped to 9 feet and missed his par putt. He had a chance for a birdie on the ninth, but his 3-footer went 180 degrees around the cup before lipping out.
'Whenever you are putting and the wind is blowing that hard it's hard to keep a good rhythm. I hit it hard and spun it around. Those things happen,' he said.
Flesch opened the back nine with consecutive birdies from 3 feet and 9 feet, but had a 3-putt bogey on the par-3 12th before closing with 5-foot birdie putts on each of the last two holes.
Two years ago at Reno, Allan led by two heading to the final hole but missed a 4-foot bogey putt for the victory. He said it will be difficult to catch the leader on Sunday.
'For him, I think a par round would be pretty good and make it tough on us,' Allan said.
Flesch, for one, hopes the wind blows just as hard.
'If I go out there tomorrow and the wind doesn't blow, it brings a whole lot more guys back into it,' he said.