Japan's Kei Nishikori is out for the rest of the season after tearing a tendon in his right wrist.
The world number nine joins 12-time Grand Slam champion Novak Djokovic and Stan Wawrinka in missing the US Open, which starts on 28 August.
Nishikori, 27, is also one of seven top-10 players to pull out of this week's Cincinnati Masters.
"Kei hit a serve during practice and heard a 'pop' in his wrist," said a statement from his manager.
"At this stage, we have elected not to do surgery and Kei is in a cast. After the swelling comes down in the next weeks, we will evaluate next steps."
Djokovic, Wawrinka, Andy Murray, Roger Federer, Marin Cilic and Milos Raonic are the other top players missing in Cincinnati.
Spain's Rafael Nadal, who is seeded first, will be the new world number one from Monday after Federer's withdrawal.
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