He defeated Juan Martin del Potro of Argentina 6-3, 7-6, 6-3 in straight sets.
Djokovic had lost five previous finals at Flushing Meadows, but he was determined to make amends for his lack of trophies in NY as his defensive ability combined with his ruthless prowess saw him break in the fourth game, although Del Potro was not in the mood to give up so easily as he hit straight back.
His first three service games were comfortable as he won 12 out of 14 points thanks to a succession of big first serves, but it all started to go wrong in game eight as Del Potro contrived to lose serve from 40-0 up to leave Djokovic to serve for the set, a chance he wasn't going to pass up.
The tension lifted in a marathon eighth game that took 20 minutes to decide, Djokovic finally holding to keep the set on serve at 4-4.
For world number three Del Potro, it was a heartbreaking experience coming in just his second Slam final, nine years after he was crowned US Open champion. But Djokovic was in no mood to hang around, winning the last three games to clinch the crown.
Djokovic was thrilled to match Sampras with a 14th Grand Slam title at the US Open Sunday, but he said it's Roger Federer and Rafael Nadal who have made him the player he is. Roger Federer of Switzerland has 20 Grand Slam titles and Spain's Rafael Nadal has 17 singles' Grand Slam trophies to his name. Del Potro, the 29-year-old Argentinian who won the 2009 Open, is back at his best after a series of wrist surgeries, ranked a career high No. 3. He almost quit tennis in 2015, after four wrist surgeries that wouldn't let him regain the form that carried him past Roger Federer to win the 2009 U.S. Open.
"I'm very sad for being a loser today", del Potro said.
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After Djokovic, 31, watched them increase their advantages over him while he went more than 2 years without a major, hampered by an injured right elbow that required surgery in February, he is now got his game in order.
Just like last night's women's singles final, the match was played under closed roof with rain in NY.
In one charge at the net, Djokovic picked a del Potro volley off his toes and sent back a victor.
Ironically, John McEnroe, who quarreled with umpires throughout his career, presented Djokovic with the trophy.
But against one of the best returners in the business, Del Potro needed to be far more assertive.
"You learn when you're down, when you have doubtful moments, when things are not working out as you want them to".
The tiebreaker was resolved thanks to more del Potro miscues on his forehand side, as he looked more and more worn out. But then he was broken in his next game.
While Simona Halep of Romania retained her top spot on the list, Germany?s Angelique Kerber moved one spot up to acquire the third position.