Nadal explained his decision in a series of tweets sent in Spanish and English on Tuesday.
"The situation is very complicated worldwide, the COVID-19 cases are increasing, it looks like we still don't have control of it," Nadal wrote.
This is a decision I never wanted to take but I have decided to follow my heart this time and for the time being I rather not travel. pic.twitter.com/8VA0aSACVy— Rafa Nadal (@RafaelNadal) August 4, 2020
The 34-year-old from Spain called sitting out the tournament scheduled to begin Aug. 31 in New York "a decision I never wanted to take," but added that he would "rather not travel."
The current No. 1-ranked woman, Ash Barty, already had announced she would be missing the US Open. The USTA's entry list announcements Tuesday noted that 2019 women's champion Bianca Andreescu is in the field -- at least for now; players can withdraw until the start of play -- but made no mention of Nadal.
The professional tennis tours have been on hiatus since March because of the COVID-19 outbreak, with play resuming for women on Monday in Palermo, Italy. The first men's event on the main tour is scheduled for later this month.
Nadal's announcement came shortly after the Madrid Open, scheduled for September, was canceled because of the pandemic.
In last year's thriller of a men's final at Flushing Meadows, Nadal edged Daniil Medvedev 7-5, 6-3, 5-7, 4-6, 6-4 in 4 hours, 50 minutes. That gave Nadal four titles at the US Open and a total of 19 across all the Grand Slam tournaments, just one away from Federer's career mark.
Federer will be absent from the US Open, too, but because of two operations on his right knee this year.
The last Grand Slam tournament contested without Federer or Nadal was the 1999 US Open -- four years before Nadal made his debut at one of the sport's four most prestigious events.
The USTA has given repeated indications it intends to go forward with the US Open, despite the spikes in cases around the United States, saying in a news release last week: "New York State continues to be one of the safest places in the country as it relates to the COVID-19 virus."
That is currently true -- although the area was a major U.S. hot spot early in the pandemic, so much so that a building at the US Open site was used as a temporary hospital.
New York hospitals saw more than 18,000 patients with COVID-19 at a time in mid-April when infections surged, and more than 750 patients with the illness died each day in hospitals and nursing homes. Those figures plunged in May, and rates of hospitalizations and new positive COVID-19 cases have been relatively stable since June.
There are still concerns about travel, as Nadal noted.
The USTA is planning a doubleheader of sorts at the Billie Jean King National Tennis Center. The Western & Southern Open, a hard-court tournament normally played in Cincinnati, was moved to the US Open site this year because of the pandemic and is scheduled to be played Aug. 20-28.
That is supposed to be followed by the US Open itself. And then, two weeks after the US Open closes on Sept. 13, the French Open is scheduled to begin in Paris, having been postponed from its usual May start.