MELBOURNE: Eight-time champion Novak Djokovic was made to sweat at the Australian Open on Wednesday as Serena Williams made serene progress in her bid for a record-equalling 24th Grand Slam title.

Women's favourite Naomi Osaka also charged through but fellow major-winners Stan Wawrinka, Bianca Andreescu and Petra Kvitova were all second-round casualties.

Djokovic was given a stern examination by America's Frances Tiafoe and dropped his first set of the tournament before recovering to win 6-3, 6-7 (3/7), 7-6 (7/2), 6-3.

"I was fortunate to get through the third set today, it was anybody's game," said the defending champion, after his win in hot conditions on Rod Laver Arena.

The top seed looked in control after taking the first set, but lightning-quick Tiafoe, who reached the quarter-finals two years ago, refused to go quietly.

The American bounced back to take a close second set but imploded as tensions rose in the fourth, receiving a code violation for an audible obscenity as Djokovic took charge.

"I thought we both played on a pretty high level. I mean, he pushed me to the very limit," said Djokovic.

The Serb is targeting a record-extending ninth title and his 18th Grand Slam trophy overall as he snaps at the heels of Rafael Nadal and Roger Federer, who top the all-time list with 20 each.

He avoided the fate of 2014 winner Wawrinka, who blew three match points in the fifth-set tiebreaker in his four-hour epic with Marton Fucsovics, who won 7-5, 6-1, 4-6, 2-6, 7-6 (11/9).

"I had some chance to finish the match, I didn't finish," said the 35-year-old Swiss, a three-time Grand Slam winner.

"I hesitated a little bit when I had the match point and I lost it."

Osaka, whose three Grand Slam titles include the 2019 Australian crown, had no such trouble in her evening match against France's Caroline Garcia, winning 6-2, 6-3 in 61 minutes.

Earlier Williams, 39, continued her quest to equal Margaret Court's all-time mark of 24 Grand Slams with a 6-3, 6-0 romp past 99th-ranked Serbian Nina Stojanovic.

Williams hit 27 winners in her 101st Australian Open match while again sporting her unique, one-legged catsuit inspired by track legend 'Flo-Jo'.

"I'm here to have fun and it's great to be playing in front of a crowd," said the American great.

With Australia virtually virus-free, the tournament is welcoming the biggest Grand Slam crowds since the pandemic, although attendances are well down on previous years.

Williams' elder sister Venus, 40, was a major casualty on day three when she painfully rolled her ankle in the first set against Sara Errani before hobbling through a 6-1, 6-0 defeat.

And Andreescu, the 2019 US Open champion who missed the entire 2020 season with a knee injury, saw her comeback come to an abrupt end 6-3, 6-2 against Taiwan's Hsieh Su-wei.

"You need to find a way to get through and the crowd helped me fight," said Hsieh after beating the Canadian, who was coming off a draining three-setter against Mihaela Buzarnescu.

Elsewhere Kvitova, the former Wimbledon champion and Melbourne runner-up in 2019, committed 44 unforced errors in her 6-4, 1-6, 6-1 defeat to Romania's Sorana Cirstea as the big names tumbled on day three.

However, reigning US Open champion Dominic Thiem, runner-up to Djokovic last year, was all smiles as he beat Germany's Dominik Koepfer 6-4, 6-0, 6-2.

"It was great, to be honest," Thiem said of his performance on Margaret Court Arena.

Eighth seed Diego Schwartzmann of Argentina also hurried into the last 32, brushing aside Frenchman Alexandre Muller 6-2, 6-0, 6-3 in an hour and 32 minutes on 1573 Arena.

Germany's volatile US Open finalist Alexander Zverev will close out the night session against America's Maxime Cressy.

The tantrum-prone Nick Kyrgios could also provide fireworks out on his favourite John Cain Arena against France's 29th seed Ugo Humbert.