On the eve of the draw for the year's final Grand Slam event that begins Monday on the Flushing Meadows hardcourts, US Open tournament director David Brewer announced the withdrawal.
"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has informed us that she will be unable to compete at the US Open this year due to a right shoulder bursitis and has withdrawn from the tournament," he said.
"We wish her a speedy recovery and look forward to her return to New York next year."
As a result, Poland's Agnieszka Radwanska moves into the third seed in the women's singles draw and other seeds will move up one place, with Russia's Anastasia Pavlyuchenkova advancing into the 32nd spot.
Sharapova's only match since a second-round defeat at Wimbledon in late June was a loss in her opening match in last week's WTA event at Cincinnati to American Sloane Stephens.
That was followed by a split with Jimmy Connors, who had been her coach for less than three weeks. Sharapova had been nursing a hip injury after Wimbledon.