The world No. 1 will have to navigate a star-studded field in order to claim his fourth New York title this summer.
Officially announced on Wednesday, the 2018 direct entry list also includes five-time champion Roger Federer, two-time titlist Novak Djokovic, 2009 winner Juan Martin del Potro, 2012 champ Andy Murray and 2014 winner Marin Cilic.
World No. 3 Alex Zverev, who has not advanced beyond the second round in three US Open main-draw appearances, will look to make his breakthrough this time around, and Kevin Anderson, a US Open and Wimbledon finalist in the past 12 months, rounds out the Top 5 entrants.
John Isner, who has achieved a new career-high ranking of No. 8 after his semifinal run at Wimbledon, will likely enter the tournament as the top-ranked American, while No. 6 Grigor Dimitrov and No. 9 Dominic Thiem complete the Top 10.
After missing out due to injury in 2017, Djokovic, Murray, Milos Raonic and Kei Nishikori are all set to return to the New York hard courts this August.
Of the Top 100 men in the ATP World Tour Rankings, Tomas Berdych is the lone player to withdraw from this year's event. The Czech will sit out due to a back injury.
The 2018 US Open main draw will be played Monday, Aug. 27, through Sunday, Sept. 9, at the USTA Billie Jean King National Tennis Center in Flushing, N.Y.
The 101 men who received direct entry into the US Open represent 40 different countries, with the United States boasting the most guaranteed entrants with 11.
In addition to Isner, the American contingent also includes world No. 14 Jack Sock, No. 28 Sam Querrey, No. 45 Frances Tiafoe, No. 48 Steve Johnson, No. 55 Ryan Harrison, No. 56 Tennys Sandgren, No. 60 Jared Donaldson, No. 65 Taylor Fritz, No. 80 Mackenzie McDonald and No. 86 Denis Kudla.
Serbia's Viktor Troicki, ranked No. 102, was the last man to receive direct entry into the field of 128. Murray is one of three men who used a protected ranking to gain entry, alongside Japan’s Yoshihito Nishioka and Germany’s Cedrik-Marcel Stebe.
The July 16 edition of the ATP Rankings was used to determine the US Open main-draw entry list, though seeds will be determined and announced closer to the start of the event.
Sixteen more players will gain entry through the US Open Qualifying Tournament, held Aug. 21-24, while the eight remaining spots are wild cards awarded by the USTA.
After combining to win six of the last seven major titles, Nadal and Federer will be among the favorites to lift the trophy this summer. Despite having met 38 times in their legendary careers, including 12 times in Grand Slams, the world's top two players have never met in New York.
As we celebrate the 50th anniversary of the US Open with special recognitions and ceremonies to honor the tradition and history of the event throughout this year's tournament, a long-awaited showdown between the two former champions could be a perfect addition to the festivities.