She posted a 12-under 130 total with one round left in the 54-hole tournament.
South Korea's Choi Na-yeon (64) and Japan's Haru Nomura (66) are one shot behind, with defending champion Anna Nordqvist lurking two back after a 68.
"My second shot was pretty good," Icher told reporters after matching the lowest score in the history of the event.
She said all of her birdies were from inside 10 feet.
"I made a lot of second shots close to the hole, so made some birdies easier to do. The greens are difficult to read ... so the closer you are, the easiest it is."
Icher, 37, is seeking her first LPGA victory.
Her task has perhaps been helped by the absence this week of many of the game's top players, including New Zealand's world number one Lydia Ko and the winner of the past three events, Ariya Jutanugarn of Thailand.
(Reporting by Andrew Both in Cary, North Carolina; Editing by Mark Lamport-Stokes)
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