Russian world No 3, who only played one match since Wimbledon exit, unable to recover from problem.
Shoulder injury forces Maria Sharapova out of US Open tennis
Maria Sharapova has withdrawn from the US Open with a shoulder injury.
A statement from US Open tournament director David Brewer said: "Maria has informed us that she will be unable to compete at the US Open this year due to a right shoulder bursitis and has withdrawn from the tournament.
"We wish her a speedy recovery and look forward to her return to New York next year."
Sharapova was seeded third for the tournament, matching her current world ranking, despite having played just one match – a loss to Sloane Stephens in the opening round of the Cincinnati Open last week – since Wimbledon due to injury.
After that match, Sharapova split from Jimmy Connors, her coach, who had only taken over from Thomas Hogstedt in July.
"I just wanted to let you know that withdrawing from the US Open has been a really tough decision to make," the 26-year-old Russian, who won in Flushing Meadows in 2006, said on Facebook.
"I have done everything I could since Wimbledon to get myself ready but it just wasn't enough time.
"I have done many tests, received several opinions and it all comes down to taking the proper amount of time to heal my shoulder injury properly.
"It's certainly not an easy decision to make ahead of one of my favorite tournaments, but I know it's the right one that will get me back on the courts soon.
"I plan on taking the next few weeks off, receiving proper treatment and rehabilitation. I will miss being part of the US Open, but can't wait for next year!"
Sharapova has suffered with shoulder injuries in the past, missing nine months after surgery in 2008. Prior to that surgery she had won Wimbledon in 2004, the US Open in 2006 and the Australian Open in 2008.
She won a fourth grand slam tournament with victory at the French Open last year.
Her withdrawal will see all the players seeded below her move up a slot, with Anastasia Pavlyuchenkova now seeded 32nd.
The draw for the US Open takes place later on Thursday, with the first round starting on Monday.
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