Defending champion Novak Djokovic suffered a shock defeat by world number 117 Denis Istomin in the second round of the Australian Open.

The six-time winner struggled for rhythm and lost 7-6 (10-8) 5-7 2-6 7-6 (7-5) 6-4 in four hours and 48 minutes.

It is the first time Djokovic, 29, has lost in the second round of a Grand Slam since 2008 at Wimbledon.

The result leaves world number one Andy Murray as favourite to win his first Australian Open title in Melbourne.

Scot Murray, who has already reached round three, has lost five finals in the last seven years, four of them to Djokovic.

It is only the second time in seven years that Djokovic has lost to a player ranked outside the top 100 – his defeat by Juan Martin del Potro, ranked 145th, at the Rio Olympics in 2016 the other occasion.

Istomin holds nerve against world number two

Djokovic could not find his rhythm, winning his first service game after 15 minutes before going on to lose the first set in one hour and 25 minutes.

He won four consecutive games in the third set as his opponent faltered but Istomin came back in the fourth set to take it to a tie break.

Both players served aggressively as they received vocal support from the crowd, with Istomin taking the match to a deciding set with a brutal ace.

Istomin, who broke in game five, remained strong on his own serve and raised his arms to the crowd after Djokovic sliced his final shot into the net.

Uzbek Istomin will next face Spain’s Pablo Carreno Busta, who beat Britain’s Kyle Edmund on Thursday.

‘I surprised myself’

“It is the biggest win (of my career) for me and means so much, now I feel I can play with these guys and be with them on the same level,” said Istomin.

“From the third set I had cramp in my leg, I don’t know how I held it. I was playing so good. I surprised myself.”

Istomin had two years out of the game after breaking his leg in a car accident in 2001 and spending three months in hospital.

Coached by his mother Klaudiya, he dropped out of the top 100 in 2016 and was given a wildcard to play the Australian Open.

Prior to his win over Djokovic, Istomin had won just one of 33 matches against a player ranked in the world’s top 10.

His best Grand Slam result is reaching the last 16 at Wimbledon in 2012 and the US Open in 2013, where he lost to Murray.