The final Grand Slam of the year gets underway on Monday and Nadal, who is currently world No 1, will be the top seed at Flushing Meadows.
Nadal is the defending champion and will be looking to keep hold of the 2000 ATP points on offer.
The Spaniard, who lifted the Rogers Cup in Toronto earlier this month, is aiming to clinch the US Open for the fourth time and get his hands on his second Major of the season.
Federer, meanwhile, who has 20 Grand Slam titles to his name, is aiming to triumph in New York for the first time since 2008.
Former US Open finalist Greg Rusedski, however, doesn’t think Federer is the favourite going into the tournament.
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He said: “I’d go Djokovic, Nadal and then Federer. I do still think he has got a shot to win it.
“At the Grand Slams he finds a way to lift his level so don’t discount him. He is probably going to get better (prior to the tournament).
“Yes he hasn’t won the US Open in many years (since 2008) but he is healthy.
“Last year everybody thought he had a chance to win the US Open and his back went out in Montreal and he wasn’t really the same.
“This year he at least comes in healthy.”
Novak Djokovic’s resurgence this year which included landing the Cincinnati Masters last weekend, sees him seeded sixth.
And Juan Martin Del Potro, the 2009 US Open champion, is seeded third and has reached a career-high No 3 in the rankings.
US Open seedings in full:
1. Rafael Nadal, Spain
2. Roger Federer, Switzerland
3. Juan Martin del Potro, Argentina
4. Alexander Zverev, Germany
5. Kevin Anderson, South Africa
6. Novak Djokovic, Serbia
7. Marin Cilic, Croatia
8. Grigor Dimitrov, Bulgaria
9. Dominic Thiem, Austria
10. David Goffin, Belgium
11. John Isner, United States
12. Pablo Carreno Busta, Spain
13. Diego Schwartzman, Argentina
14. Fabio Fognini, Italy
15. Stefanos Tsitsipas, Greece
16. Kyle Edmund, Great Britain
17. Lucas Pouille, France
18. Jack Sock, United States
19. Roberto Bautista Agut, Spain
20. Borna Coric, Croatia
21. Kei Nishikori, Japan
22. Marco Cecchinato, Italy
23. Hyeon Chung, South Korea
24. Damir Dzumhur, Bosnia and Herzegovina
25. Milos Raonic, Canada
26. Richard Gasquet, France
27. Karen Khachanov, Russia
28. Denis Shapovalov, Canada
29. Adrian Mannarino, France
30. Nick Kyrgios, Australia
31. Fernando Verdasco, Spain
32. Filip Krajinovic, Serbia