Azarenka announced her withdrawal on Monday after posting on Twitter last week that she might have to pull out of the year's final Grand Slam event.
"I am sadly unable to compete in this year's U.S. Open due to my ongoing family situation that I am working through," the 28-year-old Belarusian said in a statement on Monday.
"While I will dearly miss being in New York and playing in one of my favorite tournaments where I have enjoyed some of the best moments in my career, I am already looking forward to being back next year."
Azarenka gave birth to her son, Leo, in December and returned to the WTA Tour in June. She separated from her son's father shortly after Wimbledon and was hopeful to work out her differences with him so that she could play in the New York-based tournament without leaving her son in California.
The former world No. 1 announced via Twitter last Thursday that she and her son's father are working "to resolve some of the legal processes." The two-time Australian Open champion also noted that she would need to leave 8-month-old Leo in California while playing at Flushing Meadows, "which I'm not willing to do."
"Balancing child care and a career is not easy for any parent, but it is a challenge I am willing to face and embrace," Azarenka added. "I want to support men and women everywhere who know it is OK to be a working mother -- or father. No one should ever have to decide between a child and their career. We are strong enough to do both."
Azarenka has played in just two tournaments since the 2016 French Open. She withdrew from last week's Western & Southern Open in Cincinnati.
Japan's Misa Eguchi moves into the main draw for U.S. Open, which starts next Monday.