By Toby Prince
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, committed 57 unforced errors and saved 11-of-19 break points in his all-or-nothing assault.
“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.”
Just when the Spanish star was having a torrid time, male and female top seeds, Novak Djokovic and Serena Williams were cruising to the next round of the competition.
Williams fought back to defeat 101st-ranked US compatriot, Bethanie Mattek-Sands, 3-6, 7-5, 6-0 at Arthur Ashe Stadium and needs only four more triumphs to complete the first calendar Slam since Steffi Graf in 1988.
“I’m not trying to live on the edge,” Williams said. “I don’t think I came out too slow. I think Bethanie came out really well. I had to adapt to her game and I finally got some rhythm going toward the end of the second set.”
Djokovic moved a step closer to his 10th career Slam crown and third of the year by defeating Italy’s Andreas Seppi 6-3, 7-5, 7-5.
He said after the game: “It was a tough three sets, just hanging in there. Be patient for your opportunities. You try to cash in when they come.”