Nadal, who captured a 10th French Open title in June, will be chasing a third US Open title to go with those he won in 2010 and 2013.
Nadal, who captured a 10th French Open title in June, will be chasing a third US Open title to go with those he won in 2010 and 2013 when the final Grand Slam of the season starts on Monday at Flushing Meadows.
He's seeded first ahead of Britain's Andy Murray, with Wimbledon champion Roger Federer seeded third.
Switzerland's Federer will be seeking his 20th Grand Slam title and his sixth in New York.
But both Murray -- who won the US Open in 2012 -- and Federer have battled injuries in the build up, with the Briton sidelined since Wimbledon with a hip injury and Federer skipping the Cincinnati Masters with back trouble.
Injuries have led to a string of notable absentees, including reigning champion Stan Wawrinka and two-time winner Novak Djokovic.
Germany's Alexander Zverev, 20, is a beneficiary, ranked sixth in the world he is seeded fourth.
Former champion Marin Cilic, Dominic Thiem, Grigor Dimitrov and Jo-Wilfried Tsonga round out the top eight. John Isner is the top US man, seeded 10th.
The draw will be held on Friday at noon (1600 GMT).
Czech Pliskova, runner-up last year to Germany's Angelique Kerber, leads the women's field ahead of world number two Simona Halep.
Spain's Garbine Muguruza, who won her second career Grand Slam title at Wimbledon and claimed her first WTA title on US courts at Cincinnati, is seeded third.
Elina Svitolina, winner of the WTA event in Toronto, is the fourth seed ahead of Caroline Wozniacki and Kerber. Johanna Konta and former champion Svetlana Kuznetsova complete the top eight.
Venus Williams is the highest ranked American, seeded ninth.
Six-time US Open champion Serena Williams will be absent as she awaits the birth of her first child.
1. Rafael Nadal (ESP), 2. Andy Murray (GBR), 3. Roger Federer (SUI), 4. Alexander Zverev (GER), 5. Marin Cilic (CRO), 6. Dominic Thiem (AUT), 7. Grigor Dimitrov (BUL), 8. Jo-Wilfried Tsonga (FRA), 9. David Goffin (BEL), 10. John Isner (USA)
11. Roberto Bautista Agut (ESP), 12. Pablo Carreno Busta (ESP), 13. Jack Sock (USA), 14. Nick Kyrgios (AUS), 15. Tomas Berdych (CZE), 16. Lucas Pouille (FRA), 17. Sam Querrey (USA), 18. Gael Monfils (FRA), 19. Gilles Muller (LUX), 20. Albert Ramos-Vinolas (ESP)
21. David Ferrer (ESP), 22. Fabio Fognini (ITA), 23. Mischa Zverev (GER), 24. Juan Martin del Potro (ARG), 25. Karen Khachanov (RUS), 26. Richard Gasquet (FRA), 27. Pablo Cuevas (URU), 28. Kevin Anderson (RSA), 29. Diego Schwartzman (ARG), 30. Adrian Mannarino (FRA), 31. Feliciano Lopez (ESP), 32. Robin Haase (NED)
1. Karolina Pliskova (CZE), 2. Simona Halep (ROM), 3. Garbine Muguruza (ESP), 4. Elina Svitolina (UKR), 5. Caroline Wozniacki (DEN), 6. Angelique Kerber (GER), 7. Johanna Konta (GBR), 8. Svetlana Kuznetsova (RUS), 9. Venus Williams (USA), 10. Agnieszka Radwanska (POL)
11. Dominika Cibulkova (SVK), 12. Jelena Ostapenko (LAT), 13. Petra Kvitova (CZE), 14. Kristina Mladenovic (FRA), 15. Madison Keys (USA), 16. Anastasija Sevastova (LAT), 17. Elena Vesnina (RUS), 18. Caroline Garcia (FRA), 19. Anastasia Pavlyuchenkova (RUS), 20. Coco Vandeweghe (USA)
21. Ana Konjuh (CRO), 22. Peng Shuai (CHN), 23. Barbora Strycova (CZE), 24. Kiki Bertens (NED), 25. Daria Gavrilova (AUS), 26. Anett Kontaveit (EST), 27. Zhang Shuai (CHN), 28. Lesia Tsurenko (UKR), 29. Mirjana Lucic-Baroni (CRO), 30. Julia Goerges (GER), 31. Magdalena Rybarikova (SVK), 32. Lauren Davis (USA)