The 19-year-old Thai star followed her title win in Arkansas on Sunday - her second of the season - with an opening opening five-under 66 on Thursday.
It left the world No.3 tied second with American Lizette Salas, one shot behind the leader, China's Xiyu Lin, who made a 10-foot eagle putt on the par-5 17th hole.
Thitikul is one of two players in the field who, if victorious, can claim the No.1 ranking from Jin Young Ko, who is at home in South Korea resting an injured wrist.
The other is world No.2 Nelly Korda, and her odds took a hit when she opened with a 75.
Lexi Thompson, who has gone more than three years since her last LPGA victory, had a chance to share the lead with a birdie on her final hole at Old American Golf Club.
She took bogey and had to settle for being in the group at 67, with Englan'd Charley Hull,Thailand's Moriya Jutanugarn and Canada's Maddie Szeryk.
Young Australians Karis Davidson (70, tied 19th) and Steph Kyriacou (71, tied 26th) continued their good form from last week.
Thitikul came to life late on a firm course, running off three straight birdies. The course is nothing like the Arkansas course where she won last week, but the Thai teen is adjusting.
"Pretty firm and like every hole it's run-out, and the green, it's tricky as well," Thitikul said. "But yeah, pretty good today. Hitting pretty good. Get myself a lot of chances to make a birdie."
Lin was runner-up in Thailand in the early part of the year, and she was runner-up to Ally Ewing this month in Cincinnati.
"I think at this level my game is in a good place, and obviously I'm still trying to chase the first win," Lin said. "So I'm just going to keep trying and keep pushing myself."
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