"Unfortunately I will not be able to compete in this year's US Open," Sharapova said on her Facebook page on the eve of the event. "I have done everything possible to be ready but it was just not enough time. To all my amazing fans, I will be back in the Asian swing in a few weeks and look forward to finishing the year healthy and strong".
Ranked third in the world and seeded second at the US Open, Sharapova has not played in a tournament since losing to Serena Williams in the Wimbledon semifinal. Sharapova withdrew from the Rogers Cup earlier this month because of a leg injury.
Sharapova's US Open draw saw her potentially meeting Williams in the semifinals as Williams attempts the first calendar-year Grand Slam in nearly 30 years.
Sharapova has five majors titles to her credit, including the 2006 US Open championship, but she has not won one since the 2014 French Open.
This is the second time in three years that Sharapova has had to withdraw from the US Open.
Fellow Russian Daria Kasatkina will replace Sharapova in the draw, the USTA announced.
Information from The Associated Press was used in this report.