The U.S. Open is scheduled to start at Flushing Meadows on Aug. 31.
"I know the (at)usta and (at)WTA have worked tirelessly to put on a safe event and I wish everyone there a successful tournament," Halep wrote.
Irina Khromacheva of Russia will replace Halep in the main draw, according to the United States Tennis Association.
Rafael Nadal, the men's defending champion, has also withdrawn from the tournament, but top-ranked Novak Djokovic has said he will play. Roger Federer is out for the rest of the season after two operations on his right knee.
Stan Wawrinka, the 2016 U.S. Open champion, is also out, along with Gael Monfils and Nick Kyrgios.
Withdrawals to date:
Women
Bianca Andreescu, Ashleigh Barty, Simona Halep, Belinda Bencic, Kiki Bertens, Ana Bogdan, Fiona Ferro, Julia Görges, Hsieh Su-wei, Barbora Krejčíková, Svetlana Kuznetsova, Anastasia Pavlyuchenkova, Peng Shuai, Anastasia Potapova, Samantha Stosur, Barbora Strýcová, Elina Svitolina, Wang Qiang, Wang Xiyu, Wang Yafan, Zheng Saisai and Zhu Lin.
Men
Roger Federer, Rafael Nadal, Fabio Fognini, Pierre-Hugues Herbert, Nicolás Jarry, Nick Kyrgios, Gaël Monfils, Alexei Popyrin, Lucas Pouille, Jo-Wilfried Tsonga and Stan Wawrinka.