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.