The 28-year-old Belgian star, who has racked up four major championships in her career, told reporters she'll hang up her racquet following the Aug. 27-Sept. 9 New York event.
Three of her major titles came there.
"I will end my career at the U.S. Open," Clijsters said, adding New York "is where I enjoyed my greatest triumphs and it is a very special place for me."
Clijsters, currently recovering from a hip injury, had already indicated 2012 would be her last year on the WTA Tour. She has skipped the clay-court season to prepare for Wimbledon and the London Olympics.
She first retired in 2007 but returned in 2009, winning the U.S. Open that year as well as the next.
Celebrity Families of 2014 [PHOTOS]