The American, ranked 154th in the world, scored 13 points on a modified Stableford scoring system - awarding points for birdies and eagles and deducting them for bogeys and worse - to reach 39 points at the par-71 Tahoe Mountain Club in Truckee, California.
American Vince Whaley scored 16 points to stand just one behind Meissner on 38, with Filipino Rico Hoey third on 36 points after 15 in the third round.
Americans Max Greyserman and Patrick Fishburn were in a share of fourth on 34.
"Any time you can go into a day ahead and keep it, it's obviously a success. Feels good," said Meissner whose best PGA Tour finish in 22 starts was fifth place at Colonial in May.
Meissner sank an eight-foot birdie putt at the second hole, made a six-foot eagle putt at the par-five third and holed a birdie putt from just inside 29 feet at the par-three eighth to keep the lead.
After a 95-minute delay for lightning, Meissner made tap-in birdies at 11 and the par-three 16th to stay in front, but missed a five-foot birdie putt at 17 that would have stretched his lead.
"I'll definitely be a little bit nervous going into tomorrow," said Meissner.
Whaley, seeking his first PGA Tour crown, followed a bogey at the second hole with an eagle at the par-five third and six birdies, the last at the 18th, to finish one adrift.
"I had a horrible warm-up session and went out and played pretty good after that," Whaley said. "I felt really good. Drove it well, ironed it well. Left a few putts out there, but it was a good day."
Hoey made eight birdies against a lone bogey to grab third.
"Everything's coming together in a sense," Hoey said. "I don't feel like I'm hitting the ball great, putting it great, but I'm positioning myself in good spots and just taking advantage where I can make birdies and eagles."
