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Number one Barty, who has been in dominant form in 2022, takes on experienced Italian 30th seed Camila Giorgi to start the night session on Rod Laver Arena.
Nadal takes on dangerous Russian 28th seed Karen Khachanov late in the game, with the Spaniard warning his best is yet to come as he returns to peak form after injury in 2021.
Barty, chasing a first title at home, has barely sweated so far, dropping just three games in two matches.
The Wimbledon champion has won the Adelaide International warm-up with an untouchable serve, and he’s also been perfect so far in Melbourne.
“I continually try to weaponize it,” she said of her serve, which was unbroken for 48 consecutive games spanning five games.
“I’m not the tallest of girls, but I know I have good technique and I know if I can find my rhythm and use it effectively it can be a weapon. »
Four-time Grand Slam champion Osaka said she was improbably inspired during the first Slam of the year by Australian maverick Nick Kyrgios and Briton Andy Murray, who tweeted that he enjoyed watching her .
“It certainly means a lot. For me, that was a really cool moment,” she said of Murray’s post.
Nadal’s journey to becoming the first man to win 21 Grand Slams – he’s tied on 20 with Roger Federer and Novak Djokovic both missing – could see him meet Olympic champion Alexander Zverev in the quarter-finals.
But he must first dispatch Khachanov – with the prospect of another Russian, last year’s semi-finalist Aslan Karatsev, waiting in the last 16.
“I think playing against Khachanov is going to be a big challenge,” said Nadal, who said he wasn’t looking beyond Friday’s game.
“I never think that far ahead. Staying focused on my daily work, on what’s to come, and that’s it. A moment in time, that’s all.
Third seed Zverev will face Moldovan qualifier Radu Albot at the ‘party ground’ John Cain Arena, while Italy’s seventh seed Matteo Berrettini takes on Spaniard Carlos Alcaraz in the men’s draw.
The women’s action on Rod Laver begins with former two-time Belarusian Australian Open champion Victoria Azarenka taking on 15th seeded Ukraine Elina Svitolina.
They will be followed by French Open champion and fourth seed Barbora Krejcikova of the Czech Republic against Latvian Jelena Ostapenko.
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