Two-time champion Rafael Nadal suffered his earliest US Open exit in a decade after Italy's Fabio Fognini bested the Spaniard in a sensational 3-6, 4-6, 6-4, 6-3, 6-4 third-round victory.
The stunning result confirmed the sad, sudden decline of the 14-time major winner, who until Friday had won 151 Grand Slam matches when he had taken the first two sets.
Nadal will also finish the season without at least one Grand Slam title for the first time since 2004.
It was the 15th defeat of his miserable year, which has seen him beat just two top-10 players and where his best performances at the majors were quarter-final runs at the Australian and French Opens.
Fognini, the 32nd seed, becomes the first Italian in the last 16 at the US Open since Davide Sanguinetti in 2005 and will face Spain's Feliciano Lopez for a place in the quarter-finals.
"It was very tough against him," said Fognini, who smashed 70 winners, commited 57 unforced errors and saved 11-of-19 break points in his all-or-nothing assault.
Fabio Fognini of Italy hits a return to Rafael Nadal of Spain during their 2015 US Open third round men's singles match. Fognini has become the first man to best Nadal from two sets to love down in a Grand Slam (AFP Photo)
"It was an incredible match to come from two sets down against Rafa who is one of the best players in the world."
Fognini has now defeated Nadal three times this year but his earlier wins were on clay in Rio and Barcelona.
"After the first two sets, I said 'OK, just concentrate, keep trying and anything can happen.' The fifth set was really difficult for both of us."
Nadal had raced into a routine two sets to love lead.
He was also a break up in both the third and fourth sets.
But the colourful, sometimes controversial 28-year-old Italian rallied with some superb shot-making as the Arthur Ashe Stadium duel ticked towards and past 1am.
By the end of the fourth set, the statistics were telling.
Fognini had unleashed 50 winners to Nadal's 24 while the Spaniard had converted just five of 14 break points.
Fognini broke for 2-1 in the decider with Nadal looking increasingly punch-drunk, an appearance with which the watching Tiger Woods would have painfully sympathised.
Nadal, stretched to a five-setter at the US Open for only the second time in his career, came off the ropes to hit back for 2-2 with a breathtaking running forehand winner which had the crowd on its feet.
Fognini pounced again, breaking for 3-2, then cracked as the 14-time major winner clawed his way back for 3-3.
In a nail-biting finale, breaks were exchanged again with Fognini surrendering a 40-0 lead at 4-3.
The non-holding pattern continued as a seventh successive break, sealed with a backhand winner crosscourt, put Fognini back in the driving seat and serving for the match at 5-4.
This time he did not falter, claiming victory when Nadal hit a weary backhand wide.