World number two Novak Djokovic suffered an incredible five-set loss to Denis Istomin in a huge upset in the Australian Open second round.

The two-time defending champion at Melbourne Park was stunningly beaten 7-6 (10-8) 5-7 2-6 7-6 (7-5) 6-4 by Istomin in remarkable match on Rod Laver Arena on Thursday.

The loss marked Djokovic's earliest grand slam exit since Wimbledon 2008 as he was outdone by a red-hot Istomin in four hours, 48 minutes

The 12-time grand slam champion was below his best against Istomin, a player he had beaten relatively comfortably in their previous five meetings.

Istomin, the world number 117 who won the Asia-Pacific wildcard play-off to earn a place in Melbourne, defied his ranking with a display of incredible shot-making.

The opening game took 16 minutes in a sign of things to come, but Djokovic had to come from a break down to force a tie-break in the first set.

Djokovic took a 4-1 lead before giving up his advantage, Istomin converting his second set point as he forced his illustrious opponent into an error.

Istomin crushed 27 winners in the first set and a drop in level was expected – and came, albeit minor.

A wobbly Djokovic faced two set points in the 10th game and Istomin would rue those missed chances, the former holding then breaking before closing it out to level the match.

The third set was more like what was expected beforehand as the Serbian took control, only to give it up by quickly falling behind 3-0 in the fourth.

Brilliant defence, followed by a down-the-line winner, helped Djokovic break back before Istomin netted a forehand on set point in the 10th game.

But the Uzbek would not be denied in the tie-break, a huge ace out wide forcing a decider.

Istomin broke for a 3-2 lead in the fifth with yet another screaming winner, a backhand down the line giving him the advantage.

The extraordinary win, which set up a clash against Spaniard Pablo Carreno Busta in the third round, was completed with few nerves, Istomin serving out the match to 15.