Novak Djokovic suffered his earliest Grand Slam exit in 20 years on Sunday and said he doesn't know the solution to the physical problems he's battled in "pretty much every match" this year.

Argentine Mariano Navone's 7-6 (7/5), 5-7, 4-6, 6-2, 6-1 victory ended Djokovic's latest bid for a record 25th Grand Slam title. 

It also ended his run of 78 Grand Slam first-round victories, a streak stretching all the way back to Djokovic's 2006 loss to Paul Goldstein at the 2006 Australian Open.

Djokovic vomited on court and struggled with late-match cramps and back pain -- an "awful feeling" that he's becoming used to.

"It's something that I've been carrying, unfortunately, pretty much every match this year. Vomiting, throwing up ... Then my whole body starts to collapse, basically cramping and pain."

Although he reached the final of the Australian Open this year and the semi-finals at Wimbledon, Djokovic said he's not equipped right now to go deep in tournaments -- and he's not sure what the fix is.

"I'm just trying to address really what's going on and how far I can go this way," he said.

Despite his struggles, Djokovic appeared to have finally taken control when he broke Navone for a 2-1 lead in the fourth set with a vintage backhand winner down the line.

But Navone won the next five games, raising his arms in celebration after fighting off two break points for a 5-2 lead and breaking Djokovic again to force the fifth set.

Djokovic took a medical timeout before the final set, receiving massage on his spine and another delivery of medication.

But Navone jumped to a 3-0 lead in the decisive set and despite the urging of fans there was no road back for the Serb as his opponent dropped just one point on his own serve as he sprinted to the finish line.

"It's unbelievable," an ecstatic Navone said after triumphing in his first meeting with his longtime idol after four hours and 36 minutes.

"It was a tough match, a battle. Playing against Novak the first time in the biggest stage we have in the world of tennis right now .. Like, until 20 years he never lose in the first round, so I mean, it's crazy."

Navone, ranked 48th, was most pleased with his mental game.

"I was two sets to one down, and then break down also in the fourth, but in that moment I felt it," he said.

Djokovic broke Navone in the second game of the match as he rolled to a 3-1 first-set lead.

But he was clearly struggling and with Navone gaining confidence Djokovic had to claw out of 0-40 hole to hold for 4-1, looking weary as Navone began to extend the rallies.

Djokovic's double fault on break point allowed Navone to cut the deficit to 4-3, and after a brief pause to close the roof when showers struck, Navone held at love to knot the set at 4-4.

Neither blinked until the tiebreaker, but pills delivered by the trainer didn't solve Djokovic's sluggishness.

He fell behind 4-2 in the tiebreaker and after a cleverly angled forehand winner to make it 5-5 Djokovic hit a forehand long and another weakly into the net to give the set to Navone.

In a tense second set Djokovic missed break chances in the third and fifth games before breaking Navone at love for a 6-5 lead and holding at love to level the match at one set apiece.

- 'So grateful' -

The third set was more of the same, with Djokovic looking spent after every long rally.

He let a precious break chance go begging in the fifth game of the third and after Navone held for 3-2 Djokovic all but collapsed into his courtside chair and buried his face in a towel.

The Serb pressed on and was rewarded with a crucial break for a 5-4 lead. He held for a two sets to one lead but couldn't make the advantage stand.

After breaking Navone for a 2-1 lead in the fourth Djokovic lost the next eight games.

When it was all over, Djokovic embraced Navone, then departed blowing kisses to the crowd that had tried to will him to victory.

"So grateful to experience this," he said of the crowd support. "They were trying to lift me up in important moments ... the love and appreciation they gave me in the end really touched my heart."