Juan Martin del Potro stunned Roger Federer 3-6 7-6 (7-5) 4-6 7-6 (7-4) 6-2 to win an epic US Open final.

The sixth seed becomes the first South American player to win the top prize at Flushing Meadows since Guillermo Vilas, who was watching as his fellow Argentine triumphed on Monday, in 1977.

Del Potro told the crowd moments after his first Grand Slam title: "It is amazing for South America and amazing for me and I think this will be forever in my mind."

Federer, who secured his 40th US Open victory in a row against Novak Djokovic in the semi-finals, was bidding to become the first man since Bill Tilden in 1925 to win a sixth successive title in New York but he appeared agitated during the contest and was not at his best as Del Potro moved closer to victory.

"I would like to congratulate Juan Martin. He was the best. Of course I would have loved to win but five or six years ago I never thought I would win 40 matches in a row here," Federer told the crowd in the post-match ceremony on the Arthur Ashe Stadium.

It was the Swiss who started the match on the front foot as he bagged five break points in Del Potro's opening service game before securing the early advantage with a scintillating forehand winner.

The rest of the opener went on serve as Federer wrapped up a 6-3 success with a well-placed ace. The second set, however, was anything but predictable.

It looked like the world number one was set to take a two-sets-to-love lead until an incident involving a paper cup, with the score at deuce as Federer prepared to take a 3-1 advantage, changed the momentum of the match.

Although Federer won that game, the flow of the contest changed.

The sixth seed got himself right back into the final as he broke back as the Swiss served for the set with two superb passing shots down the line.

Del Potro was now firmly in the ascendancy and he took full advantage to level the scores with a powerful forehand winner, one of 37 he produced during the epic clash, to seal a 7-5 success in the tie-break that followed.

The final two games of the third set produced some real drama as Federer saved a break point to take a 5-4 advantage but what followed was an extraordinary outburst at the umpire during the change of ends.

The 28-year-old was clearly unhappy with the role the challenge system was playing and he lost his cool by producing a couple of expletives after he was told to end his verbal tirade by the umpire.

Federer regained his composure in the next game as Del Potro chose the worst possible time to throw in a double fault, one of 17 during the contest, as he handed a two-sets-to-one lead to the Swiss on a plate.

Both players finally won some service games with ease at the start of the fourth set until Del Potro, beaten six times in previous meetings by Federer, broke to love to take a 3-2 advantage.

The next game contained one of the points of the match as the Argentine sent a despairing forehand down the line for a winner and preceded to 'high five' the front row of the crowd. However, the defending champion was not giving up without a fight and he won the next three games in a row to get the set back on serve.

A fourth set tie-break was now on the horizon and it didn't disappoint. Federer handed the initiative straight to Del Potro with a double fault and it was all downhill from there for the Swiss.

The reigning French Open and Wimbledon champion had another dispute with the umpire over the challenge system before he sent a shocking forehand out on the full to take the match into a fifth set.

Del Potro was quick to take a crucial advantage in the final set as he broke Federer, who could only manage a 50 per cent first service rate during the match, in the defending champion's opening service game with a crunching crosscourt forehand winner.

The 20-year-old was now in control and he maintained his advantage before securing his first Grand Slam title on his third championship point as Federer sent a forehand long after four hours and six minutes of the epic encounter.

Del Potro, who is only the second man to beat Federer in a Grand Slam final, was emotional after the match as he cried during a speech in Spanish to his fans but first he was quick to pay tribute to the defeated former champion.

"One of my dreams is to win the US Open and one is to be like Roger. One is done but I will need to work hard to do the other," he said.