Djokovic won a pulsating final at Flushing Meadows in four sets to claim an incredible third grand slam title of the year and fourth of his career.
The Serbian has now beaten Nadal in six finals this season and the 6-2, 6-4, 6-7 (3/7), 6-1 victory means he has won 64 of his 66 matches in 2011.
Nadal, who looked to be back in the match after winning the third set on a tie-break, said: “Obviously I’m disappointed but this guy is doing unbelievable things so congratulations Novak and your team for everything. What you did this year is probably impossible to repeat. I try my best in every moment, these kind of matches are very difficult, it brings your body to the limit.
“I tried to play great but he always makes a fantastic comeback. That’s tennis, I tried my best and am happy with what I did. I ran to every ball and fought until the last ball.
“This year I lost a lot of finals against him but I won a lot in the past and the only thing I can do is try my best every day to keep improving and for sure I will come back next year and try my best.”
Djokovic now holds the Australian Open, Wimbledon and US Open titles after becoming only the sixth man in the open era to win three of the four majors in the same year.
The 24-year-old spent most of his acceptance speech paying tribute to the victims of the September 11 terrorist attacks after Sunday’s tenth anniversary.
But speaking about his achievements, he added: “It’s an incredible, incredible feeling. I’ve had an amazing year and it keeps going but every time I play Rafa it’s a big challenge and I want to congratulate him on a great tournament.
“I wish we have many more tough matches in upcoming years.”
Djokovic looked set for a more comfortable win when he led 6-5 in an epic third set featuring numerous breaks of serve, only to be broken again and forced into a tie-break.
Nadal stormed into a 5-1 lead and, after Djokovic dragged it back to 5-3, some questionable shot selection from the Serbian gave Nadal three set points, the first of which he converted when Djokovic powered a forehand into the net.
Djokovic received treatment for an apparent back problem before the start of the fourth set and took a full medical time-out after holding serve in the opening game.
But with everything now seemingly in Nadal’s favour, Djokovic defied the odds to break for a 2-0 lead on his fifth break point – his second having gone begging when a broken string sent a forehand sailing long.
The Serb was rejuvenated and broke Nadal again in the sixth game for a 5-1 lead and a second chance to serve out for the title. This time there was to be no mistake and a forehand winner sealed a dramatic and hard-fought victory.