The nine-time LPGA Tour winner chipped in for birdie on the par-4 13th in her bogey-free round on Kingsmill's River Course. She had a 16-under 197 total, the lowest 54-hole score in the history of the event.
"I haven't won in two years. That feels like forever, but it also feels like yesterday when I did just win, so it's kind of a give or take," Creamer said. "I've been in contention a lot, so it's not that I'm not used to this, that's for sure.
"No matter what happens tomorrow, I'm just going out there and continue what I've been doing this whole year and it's just starting to come together and one round isn't going to make or break it, that's for sure."
Second-round leader Jiyai Shin was second after a 69.
Shin also is winless since 2010.
"Well, I think when I following the leader, it makes me feel better because I knew the target," Shin said. "When I started on the leader, when I miss the shot, it make more pressure. So I really very comfortable with my position at the moment."
Dewi Claire Schreefel and Danielle Kang were 12 under. Schreefel had a 69, and Kang shot 70.
Second-ranked Staci Lewis was 11 under along with Ai Miyazato and Azahara Munoz. Lewis shot a 68, Miyazato had a 67, and Munoz a 69. Lewis and Miyazato
Two strokes behind Shin entering the round, Creamer birdied Nos. 3-5, added a birdie on the par-4 11th, chipped in on 13 and made her sixth birdie of the round on the par-5 15th.
"I hit the ball really well." Creamer said. "I gave myself tons of opportunities, and when I did get into a little bit of trouble I just kind of took my medicine and scrambled out some pars. Just hitting it really solid, so I'm able to go at a lot of these flagsticks and giving myself within 10 feet on a lot of holes. You're not going to make all of them, but you'll make most, especially with the confidence that I have right now in my putting."
Shin bogeyed the par-3 second hole and par-4 fourth, then rallied with birdies on Nos. 8-9 and 11-12.
"It was a long tough day," Shin said. "The wind made it really tough to play the course."
This is the eighth LPGA tournament at Kingsmill. All six winners—Cristie Kerr won twice—from 2003 to 2009 have at least one major championship on their resumes. Creamer and Shin also are major champions.
"I think you have to be a great ball-striker around here. You have to be really good with controlling your shots," Creamer said. "It's just one of those golf courses that you've got to be on your game. I'm sure it's going to be pretty exciting. Some great players are all kind of bunched in there, and I'm going to have to take care of my own game."