The 28-year-old Romanian withdrew hours after the defending champion Bianca Andreescu said she would not play at the Grand Slam event which starts on 31 August at Flushing Meadows.
In July, the world number one Ashleigh Barty was the first big name on the circuit to pull out of the competition citing fears about the coronavirus.
The 24-year-old Australian was soon joined by three other top 10 players Elina Svitolina, Kiki Bertens and Belinda Bencic.
In the men’s draw, the world number two Rafael Nadal said he would not defend his title for health reasons and on Monday the 2014 US Open finalist, Kei Nishikori, stood down after testing positive for the coronavirus.
"After weighing up all the factors involved and with the exceptional circumstances in which we are living, I have decided that I will not travel to New York to play the @usopen," tweeted Halep.
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— Simona Halep (@Simona_Halep) August 17, 2020
After weighing up all the factors involved and with the exceptional circumstances in which we are living, I have decided that I will not travel to New York to play the @usopen
I always said I would put my health at the heart of my decision
The former women's world number one Serena Williams, seeking a 24th career Grand Slam title to match Margaret Court's record, will compete, as will the men's world number one Novak Djokovic.
The only other players from the WTA top 10 remaining in the tournament are world number three Karolina Pliskova, reigning Australian Open champion Sofia Kenin, who is ranked fourth in the world, and Naomi Osaka, who occupies 10th place.
New York was one of the worst affected cities in the United States when the coronavirus first spiked in March and April. A temporary hospital was established on the indoor courts at the US Tennis Center.
