Djokovic had a battle on his hands after losing a first set tie-break 10-8 to trail Istomin, but the six-time winner looked to be back on track by winning the next two sets of the tie.

But his opponent refused to go quietly, with Istomin again edging out the world number two in a tie-break to force the match into a decider.

Istomin then put the Serbian on the brink of his first second round defeat at a Grand Slam event since Wimbledon 2008 when he broke in game five of the final set.

The Uzbekistan player continued to serve impressively, as he had done throughout the contest, to secure a 7-6, 5-7, 2-6, 7-6, 6-4 victory.

Istomin, who has reached the third round in Australia on two previous occasions, in 2010 and 2014, was delighted with the win.

"First of all I feel sorry for Novak. I was playing so good today," Istomin said to Jim Courier during his on-court interview after the match finished.

"So much emotion on my mind so I cannot hold it you know but I want to say thanks very much for coming to support me."

After the defeat, Djokovic praised his opponent.

"All the credit to Denis for playing amazing, he deserved to win," he said.

"I was not pleased with my performance. 

"It was just one of days when you don't feel that great and the other player is really feeling the ball, that's sport."

With Djokovic suffering an early exit, Britain’s Sir Andy Murray is now the clear favourite to secure his first Australian Open title.

Murray has been the runner-up on five occasions, with four defeats having come at the hands of Djokovic.

Six-time women's champion Serena Williams cruised into the third round, with the American beating the Czech Republic's Lucie Safarova 6-3, 6-4.

Poland's world number three Agnieszka Radwanska, however, fell to defeat.

Having narrowly won her first round tie, Radwanska was beaten 6-3, 6-2 by Croatia's Mirjana Lucic-Baroni.