summer's US Open series, stands within two of the all-time mark of 14 major titles held by Pete Sampras.
Federer also became the first man to win Wimbledon and the US Open in the same year for four consecutive years. He also joins Bill Tilden from the 1920s as the only other man to win the event at least four times in a row.
The top seed, who also owns the 2007 Australian Open and Wimbledon titles, could not fault his third victory from four matches this season against Djokovic, who beat him last month in the Montreal final.
'I thought I played well when I had to. I've played better matches in the past, no doubt. But it's a big moment, a lot of pressure for both of us,' said the winner.
'It was a bit windy again today. And the opponent plays a role in how good you can play. He made it hard to me in the beginning. All in all, I'm very happy with my performance.'
Djokovic held leads in the first and second sets but was unable to convert on a total of seven set points - five in the first, two in the second.
In the end, Federer's pressure break of the third seed in the final game spelled the end.
'I was just holding my serve and trying to wait for my chances, opportunities. I got them, and in the end I didn't use them,' said Djokovic.
Even Federer admitted to nerves: 'I felt the pressure. I've had an upset stomach, shaky hands, I've had it all. But it is just great to be back in a Grand Slam final and win it. I really enjoyed today and the entire two weeks.
'Novak deserved better than that. He's had a fantastic run, not only this tournament but the entire year. I told him at the net 'Keep it up.' We're going to have many more battles, I think.'
The victory was Federer's 27th in a row at Flushing Meadows, where he last lost in 2003.
During his win streak, Federer has lost dropped 10 sets and has only been extended to a fifth set once, against Andre Agassi in the 2004 quarter-finals. He stands 38-4 lifetime in New York.
Federer was playing in his 10th straight Grand Slam final.
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