The world No.117, who had never before beaten a top-10 player at a major, aggressively went after the second seed from the outset before sealing the 7-6 (10-8) 5-7 2-6 7-6 (7-5) 6-4 victory in four hours and 48 minutes on Thursday.

It’s the first time 12-time grand slam champion Djokovic has failed to make the third round of a major since Wimbledon in 2008.

“I feel sorry for Novak, (but) I played really good,” the 30-year-old Istomin said.

“I surprised myself.”

Djokovic reacts during his round two exit. Photo: Filip Singer / EPA

Istomin, who warmed up for the Australian Open at the $70,000 Bangkok Challenger, was on the attack from the outset.

Cramp set in during the third set but the Uzbek, who won entry to the tournament through the Asia-Pacific wildcard playoff, remarkably responded in the fourth.

At 2-all in the fifth, Istomin – metres behind the baseline – lashed a crosscourt backhand past Djokovic.

It set up what turned out to be the only break of the deciding set.

The giant-killer next faces 30th seed Pablo Carreno Busta of Spain.

Bernard Tomic will fly the flag today as the last Australian man standing in the Open.

The 24-year-old, who has made the fourth round in his last two appearances at Melbourne Park, will gun for a third when he takes on resurgent Brit Dan Evans.

Tomic is the sole survivor amongst the locals in the men’s draw following last night’s elimination of Jordan Thompson by eighth-seeded Austrian Dominic Thiem.

Thompson again showed his fighting spirit but fell 6-2 6-1 6-7 (8-6) 6-4.

Tomic, seeded 27, takes on Evans on Hisense Arena in an afternoon match.

He said that Evans, ranked world No.51,was a tricky proposition.

They have split the results in their previous two meetings but Evans has been in good form, making the final of the Sydney International earlier this month.

In his second round Evans stunned seventh seed Marin Cilic for biggest win of his career.

“Evans is not easy to play,” Tomic said.

“He’s awkward … He goes for it and he has nothing to lose.

“He’s playing the best tennis of his life at this stage. He deserves to be in the third round.”

In the women’s draw comeback queen Ashleigh Barty faces a third round tussle with German qualifier Mona Barthel, with the pair lining up in the first night match on Rod Laver Arena.

Local star Barty is looking to extend her best singles run at a major. Barthel shocked 2016 Olympic champ Monica Puig from Puerto Rico 6-4 6-4 on Wednesday, while Barty also advanced in straight sets against American Shelby Rogers.

Barty’s previous best grand slam results have come in doubles, reaching the title match at the Australian Open, Wimbledon and the US Open in 2013 alongside great friend Casey Dellacqua.

Meanwhile, Daria Gavrilova has declared she’s a better player than during last year’s charge to the Australian Open fourth round.

But the 22-year-old Australian is refusing to get carried away with her title prospects despite reaching the third round with a hard-fought 6-2 1-6 6-4 win last night over Croatian teen Ana Konjuh.

She joins Barty in the last 32.

Ranked No.23, Gavrilova next faces Swiss 12th seed Timea Bacsinszky, who she has beaten both times they have played.

With the 2016 Australian Open her best result at a grand slam, Gavrilova said she was trying not to get ahead of herself.

“I’m not thinking about the future. I’m just being in the moment right now,” she said.

Asked whether she was playing better this time around, Gavrilova said: “I think I’m a better player, yeah.”

The Hisense Arena encounter was a rollercoaster with Gavrilova breaking Konjuh in the first game of the final set and holding on to serve out the match.

Gavrilova said she was pleased with the way she kept her cool when momentum swung Konjuh’s way mid-match.

The feisty baseliner famously unravelled in a fourth-round capitulation last year from 6-0 2-0 up against Spanish top-tenner Carla Suarez Navarro.

She felt her physical game, as well as mental strength, was tracking well.

“I’m happy with the way I’m playing right now,” Gavrilova said.

“There’s nothing much to improve – just a few tactical things against players that I’m playing.”

-AAP