Thitikul led an all-Thailand finish, with Arpichaya Yubol (67) and Chanettee Wannasaen (63) tying for second at Columbia Edgewater Country Club on Sunday (Monday AEST).
American Sophia Schubert, the 54-hole leader, had to settle for a 71 and fourth place.
The 23-year-old Thitikul won for the 10th time in her LPGA career, making her the eighth player to reach 10 wins or more before turning 24. She also joined Nelly Korda as three-time winners this year on the tour.
"It's mean a lot. I would say every win it's mean a lot to the sacrifice that we put in, the work that we put in," Thitikul said after the victory.
"... (I've) had a time that I have a doubt, like, 'What is going on in my games?,' and then when you get it you're just like, 'Wow, this is what you're waiting for.'"
The world No.2 finished at 22-under 266 and won $US300,000 ($A425,000), moving her closer to $US20 million ($A28 million) in career earnings.
France's Celine Boutier (66), Pajaree Anannarukarn (67) and South Korea's Narin An (69) tied for fifth at 16 under, while American Rose Zhang (68) shared eighth at 15 under with another Thai Suvichaya Vinijchaitham (66).
Robyn Choi (71) was the best of the Australians at nine under, while Grace Kim (77) finished two under.
Thitikul, who added the Portland title to victories earlier this season at Honda LPGA Thailand and the Mizuho Americas Open, took pride in the growing presence of Thai players near the top of LPGA leaderboards.
"Yeah, like we have a lot, a lot of talented players and then I definitely believe that we can be on the top of the leaderboard," she said.
"It just matter of the time, and I just really want to inspire the next generation of Thai as well."
With Reuters & AAP.
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