Wagner shot a 6-under 64 Saturday to take a two-stroke lead after the third round of the Greenbrier Classic.
Wagner was at 14 under on the Old White TPC course. Jimmy Walker also shot 64 and was second at 12 under.
Wagner has yet to post a top 10 finish this year. At the Greenbrier, he broke a string of seven consecutive early exits.
In his two previous tournaments, he had three birdies combined. He had seven of them on Saturday.
"I felt really comfortable all day," Wagner said. "I hit a lot of good golf shots. I've got a really clear picture of what I'm trying to do on every swing.
"Sometimes when you're playing bad, you forget who you are and you get down on yourself. The last couple of weeks, I've just trying to be positive and remember that I've won three times out here. I'm a little more comfortable with myself right now."
Wagner played golf at Virginia Tech less than two hours from The Greenbrier resort. Several members of his wife's family have joined them for the weekend, and hoots from Hokies fans could be heard around the golf course.
"It's great seeing a bunch of maroon-and-orange in the crowd," Wagner said.
He hopes they can see him wrap up his first win since the 2012 Sony Open.
The other two times Wagner held the lead going into the final round on tour, he won the 2008 Houston Open and the OHL Classic at Mayakoba in Mexico.
But no third-round leader has gone on to win the Greenbrier Classic, now in its fourth year. The tournament has been decided by playoffs the past two years, and Stuart Appleby shot 59 in the final round to win by a stroke in 2010.
Wagner said he isn't going to stop being aggressive Sunday unless the wind picks up.
"I'm just going to try to make as many birdies as I can," he said. "This golf course, when it's firm and fast, may be one of my favorite places we play on tour."
Like Wagner, Walker also gets a cozy feeling at The Greenbrier. He finished one stroke out of a playoff in the 2011 Greenbrier Classic and tied for fourth in 2010.
"The golf course really seems to fit my eye," Walker said. "I like the tee shots, I like the second shots, and I feel comfortable. And when you feel comfortable at places ... I seem to play well."
Still searching for his first tour win, Walker woke up sick early Friday morning and still wasn't feeling well Saturday.
His swing certainly didn't suffer.
After seven straight pars on the front nine, Walker ran off five birdies down the stretch, including a 17-foot putt on the par-3 18th.
Walker is hoping to secure a spot in the British Open in two weeks. After the Greenbrier Classic, the leading five players not already exempt from inside the top 20 in the FedExCup points standings will earn a spot at Muirfield. Walker is 24th.
"I have a room booked," Walker said. "I might as well go use it."
Sweden's Jonas Blixt was four strokes behind Wagner at 10 under after shooting 67. Australians Matt Jones (66) and Steven Bowditch (69) and Texas teenager Jordan Spieth (67) were at 9 under.
Spieth overcame two early bogeys with birdies on three of the final four holes.
A win would give him his PGA Tour membership and make him eligible for the FedEx Cup playoffs. He's won more than $1.1 million this year and is assured of a tour card when the new season starts in October.
Among six golfers at 8 under included Bill Haas, the winner at Congressional a week ago.
Second-round leader Matt Every bogeyed the first two holes and quickly fell off the leaderboard. He shot 74 and fell into a tie for 27th at 5 under.
Ten players were trimmed from the field after Saturday's round; 81 players had advanced after Friday's play.