Ariya, who had to rise at 4 a.m. to complete the weather-delayed second round at Shoal Creek before cracking on with her third round, carded a five-under-par 67 for a 12-under 204 total and a healthy cushion over Sarah Jane Smith (74).
South Korean Kim Hyo-joo (68) was another two shots back in third place on a day when nobody could make a sustained challenge at the two frontrunners.
"I think I'm going to sleep pretty well because I didn't sleep much last night and I'm so tired right now," said Ariya, who started the third round three strokes adrift of Australian Smith.
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Victory for the Thai would give her a second major title after her 2016 Women's British Open triumph, and break the recent dominance at the U.S. Women's Open by South Korean and American players, who have claimed the past 11 tournaments.
Ariya used her prodigious power to muscle her favourite three-wood tee shots past Smith's drives with regularity, and displayed a deft short game in a round that included only one blemish, a bogey at the par-three 16th.
Smith, who failed to land a single birdie but remains Ariya's closest pursuer at eight-under 208, said the Thai was a "spectacular player".
"She hits it a long way but her short game is impeccable," added the world number 97, who is winless in 222 starts on the LPGA Tour.
"She rolls the ball beautifully. She's just the whole package. It was fun to watch her play.
"I know Ariya is going to have a great day. That is a given," she added.
"I'm going to need a really good day to have a chance."
Ariya said she had some weaknesses in her game, but was stumped to name them.
"Wait, I'm thinking," she said. "I'm not sure what, but I'm pretty sure I have.
"I'm pretty sure tomorrow is going to be a good day, even though I don't know what the outcome is going to be."
The second round, which was interrupted by a long lightning delay, was completed earlier on Saturday.
Ariya, who had 10 holes left, trimmed the margin from four shots to three before grabbing a quick lunch and getting back to work.
Two early birdies brought her to within a shot of Smith, who bogeyed the eighth and ninth holes to surrender the lead. It was a masterclass at times from Ariya, one of the highlights being a four-iron approach at the par-five 11th that covered the pin and led to a tap-in birdie.
(Editing by Clare Fallon/Peter Rutherford)
