Paula Badosa also withdrew because of injury, meaning Venus Williams needs a new opponent for her first-round match.
Both players will be replaced in the women’s singles bracket by a player who qualified for the field or lost in qualifying.
The U.S. Tennis Association announced Andreescu's withdrawal but did not specify the nature of the injury. However, when she withdrew from the previous tournament, in Cincinnati, Andreescu posted on social media that she had a small stress fracture in her back.
Andreescu was supposed to face Lesia Tsurenko in the first round in New York.
Play begins Monday at Flushing Meadows.
Andreescu is a 23-year-old from Canada who has been ranked as high as No. 4 and is currently No. 51.
She won the U.S. Open as a teenager by beating Serena Williams in the final four years ago. That made Andreescu the first player to win the women's title in New York in her tournament debut.
Badosa was ranked No. 2 last year but is now No. 46. Venus Williams received a wild card to play in the tournament at 43 where she won two of her seven Grand Slam singles titles.
AP tennis: https://apnews.com/hub/tennis