Japan's Osaka stunned the tennis world when she quit the clay-court major in Paris in May following her first-round match after being fined and threatened with disqualification when she refused to attend mandatory post-match press conferences.
The world number two, who said she had social anxiety, also skipped Wimbledon but is scheduled to play at the Tokyo Olympics and then in Montreal next month.
Osaka will be part of a women's field at the U.S. Open that will also include world number one Ashleigh Barty, who lifted her second major title at Wimbledon earlier this month.
In the men's section, former champions Novak Djokovic, Roger Federer, and Rafael Nadal -- currently tied for the men's record of 20 Grand Slam singles titles -- will resume their quest for more silverware in New York.
World number one Djokovic, fresh from his third major triumph of 2020 at Wimbledon, is aiming to become the first man since Australia's Rod Laver in 1969 to complete a calendar-year sweep.
Another former champion, Andy Murray, who is currently ranked 104, failed to make the main draw but remains the first player on the alternate list.
The U.S. Open will be held with 100% fan capacity from August 30 to September 12.
The July 19 edition of the World rankings was used to determine the US Open main draw entry list. Seeds will be determined and announced closer to the start of the event.