The victory in New York is Nadal's second US Open championship and his 13th overall major title to go with one Australian Open, eight championships at Roland Garros and two triumphs at Wimbledon.
The 13 Grand Slam wins has Nadal just one behind Pete Sampras' 14 major wins and only four behind Federer's 17, and clearly Nadal has plenty more left in him than the 32-year-old Federer.
Even though Nadal lost the second set, he claimed the victory in four 6-2, 3-6, 6-4, 6-1 and compared to some previous battles, that he has won now 22 of 37, with Djokovic it was a relatively comfortable triumph for the 27-year-old Spaniard over the world No. 1 Serb.
It was a controlled and efficient performance from Nadal who hit 27 winners to 20 unforced errors, came to the net effectively winning 17-of-23 points there and also did well on break points against Djokovic's serve, winning 7-of-12 points.
Meanwhile, Djokovic had 53 unforced errors to 46 winners and converted just three of 11 break points on Nadal's serve.
All that added up to Nadal winning in four sets in three hours and 21 minutes.
For Nadal it caps off a terrific 2013 in Grand Slams after he began the year battling a knee complaint that he wasn’t sure would ever allow him to get back to his best. Obviously he has been able to.
"For a few things this season is probably the most emotional one in my career. I felt that I did everything right to have my chance here and you play one match against one of the best players like Novak, the No. 1 in the world, so I had to be perfect to win here on his favourite surface," Nadal said.
"It means a lot for me to have this trophy, it's just amazing and I am very, very happy. It really is a special moment for me."
The loss for Djokovic is second straight Grand Slam final defeat after losing at Wimbledon to Andy Murray, and it's also back-to-back US Open losses in the final after he also went down to Murray in last year's decider.
Remarkably, it is the fourth straight final at Flushing Meadows for Djokovic, but he has just the one crown to show for it when he beat Nadal in 2011, but he lost to Nadal in 2010, Murray in 2012 and Nadal this year. He also lost the 2007 US Open final to Federer.
Djokovic remains the world No. 1, though, and should see out 2013 there, he was disappointed to miss some chances he had in the third set that could have seen him go up two sets to one, and could have made things decidedly different.
"It was disappointing that I dropped the third set even though I felt like especially in the first four or five games I was the one who was dictating the play," Djokovic said.
"But it's all my fault. I made some unforced errors in the crucial moments with forehands and dropped the serve twice when I should not have. Then all of a sudden it's two sets to one for him and he started playing much better after that. I obviously could not recover after losing the third set.
"It's the US Open final and in the end of the day I have to be satisfied with making the final even though I would have loved to win this match but it was obviously that in the important moments he played better tennis and that's why he deserved to win. I congratulate him and move on."