The Spaniard said on Twitter: "After many thoughts I have decided not to play this year’s US Open. The situation is very complicated worldwide, the COVID-19 cases are increasing, it looks like we still don’t have control of it."
- Madrid Open cancelled amid Covid-19 concerns
- US Open: Who's in and who's out? Will Djokovic, Serena and others play?
The US Open is scheduled to start on August 31 at Flushing Meadows in New York, with organisers adamant the Grand Slam will go ahead behind closed doors despite USA being the worst-hit country regarding coronavirus, with more than 150,000 deaths and 4.8m confirmed cases as of August 4.
Women's world number one Ash Barty has also withdrawn from the event, so too Nick Kyrgios, and Nadal - who won his 19th Grand Slam when winning the US Open last year - admitted it was a decision he "never wanted to take".
Rafael Nadal: If US Open was today, I wouldn’t travel
Nadal added: "We know that the reduced tennis calendar is barbaric this year after 4 months stopped with no play, I understand and thank for the efforts they are putting in to make it happen. We have just seen the announcement of Madrid not being played this year.
"All my respects to the USTA, the US Open organisers and the ATP for trying to put the event together for the players and the fans around the world through TV. 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.”
Nadal will be expected to take part in September's French Open, with the 34-year-old chasing a 13th Roland Garros title.
US Open entry list confirmed
Nadal's withdrawal came as the US Open confirmed its entry list, with world number one Novak Djokovic heading up the men's entrants.
Joining Djokovic among the Top 10 men are No. 3 Dominic Thiem, No. 5 Daniil Medvedev, No. 6 Stefanos Tsitsipas, No. 7 Alexander Zverev, No. 8 Matteo Berrettini and No. 10 David Goffin. Roger Federer is injured and out for the rest of 2020.
With Barty out No. 2 and two-time Grand Slam winner Simona Halep is the highest-ranked female player. From the top 10 there is also No. 3 Karolina Pliskova; No. 4 Sofia Kenin, No. 5 Elina Svitolina; defending champion and No. 6 Bianca Andreescu, No. 7 Kiki Bertens; No. 8 Belinda Bencic; No. 9 Serena Williams, a six-time US Open and 23-time Grand Slam champion, and No. 10 Naomi Osaka, the 2018 winner.
Eight additional Grand Slam champions are entered into the field, Petra Kvitova, Garbiñe Muguruza, Angelique Kerber, Svetlana Kuznetsova, Jelena Ostapenko, Victoria Azarenka, and two-time US Open winner Venus Williams.