Bertens, rebounding after a quick first-set loss, outlasted Romania's top seed in an exhausting second set tiebreaker, then won five of the final six games in the decider to lift her sixth career title, after five previous triumphs on clay.
"I cannot find words for this moment. I'm so happy," a tearful Bertens said on court.
The victory was the 26-year-old Bertens' first ever over a world number one and her sixth consecutive triumph over a top-10 opponent. It will see her move up to number 13 in the world rankings.
Simona Halep of Romania congratulates Kiki Bertens of Netherlands after their match during the women's final of the Western & Southern Open at Lindner Family Tennis Center on August 19, 2018 in Mason, Ohio.
Image credit: Getty Images
It also ended a nine-match winning streak by Halep, who lost in the Cincinnati final for a third time.
"Maybe once I will win one because I love to play here," said Halep. "I was a little bit tired this week but it was a pleasure to come here and play.
"Definitely, I want to congratulate Kiki. You played amazing and you definitely deserve this title."