"I really wanted to play it and I saw that many fans bought tickets to see me here, but I feel very sore with my Achilles, and I need some rest," Halep, who has not competed in the event since 2014, said in a statement released by the tournament.
"I had so many matches in the last two weeks, so it's tough. See you next year, and all the best."
Halep, who lost in three sets to Dutchwoman Kiki Bertens on Sunday in Cincinnati, was scheduled to play on Tuesday in New Haven where she won the title in 2013.
"Hopefully Wednesday or Thursday I can get back on the court," Halep, 26, told reporters. "I need to physically rest and to emotionally and mentally rest. I'll see day by day how it goes."
Halep said the injury is a recurring issue that forced her to miss time earlier this season, including the Wimbledon tune-up at Eastbourne.
"I've had it for a long time," said Halep. It's (been) bothering me, but I have to go through it."
The U.S. Open in New York runs Aug. 27-Sept. 9.
(Reporting by Frank Pingue in Toronto; Editing by Ian Ransom)
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