The Pole has won five Grand Slams but her best performance at Melbourne Park is the semi-finals in 2022.
“For sure it wasn’t an easy first round, so I’m happy that I’m through,” said Swiatek.
In-form world number three Gauff laid down a marker as she swept aside former champion and fellow American Sofia Kenin on Rod Laver Arena.
The third seed, who is unbeaten this year after leading the US to United Cup glory, eased past the 2020 Melbourne Park winner 6-3, 6-3 in 80 minutes.
“I knew it was going to be difficult, but you know, I’m happy with how I played,” said Gauff, the 2023 US Open champion.
Victoria Azarenka, the 2012 and 2013 champion in Melbourne, was a notable early loser as the Belarusian lost 6-2, 7-6 (7/2) to Italy’s Lucia Bronzetti.
The 11th-seeded Tsitsipas also crashed out at the first hurdle when young American Alex Michelsen blasted past him 7-5, 6-3, 2-6, 6-4.
The 26-year-old Greek, who played Novak Djokovic in the 2023 final at Melbourne Park, never looked comfortable against the 20-year-old Michelsen who had him running all over the court.
“I just tried to stay super composed out there today, I knew it was going to be a battle to the end,” said the 42nd-ranked American, who scored his first win over a top-20 player at a Slam.
Serbian great Djokovic is hoping to roll back the years and win an 11th Australian Open and record 25th Grand Slam singles title.
He faces the American Nishesh Basavareddy in the prime-time evening match on Rod Laver Arena.
“To be honest, I don’t know much about him,” said Djokovic, who is now coached by former rival Andy Murray.
“I’m sure that he is going to be really pumped to make a statement.”
‘Good to be back’
He will be preceded on court by world number one Sinner with the Italian aiming to put a doping scandal behind him when he opens his title defence against Chile’s Nicolas Jarry.
Sinner is under a cloud after twice testing positive for traces of the steroid clostebol in March.
While exonerated by the International Tennis Integrity Agency, the World Anti-Doping Agency appealed and his case which will be heard by the Court of Arbitration for Sport on April 16-17. Sinner denies wrongdoing.
Spain’s Alcaraz is bidding to complete a career Grand Slam of all four majors aged just 21 and begins against in-form Kazakh Alexander Shevchenko in the night session on Margaret Court Arena.
The four-time major winner Alcaraz has never gone past the quarter-finals in Melbourne.
Japan’s Naomi Osaka, a two-time former Australian Open champion, will wrap up the evening on centre court against the 67th-ranked Caroline Garcia.
It is a repeat of last year’s first-round clash that the French player won.
Now ranked 51, Osaka won two of her four Grand Slam titles to date at Melbourne Park in 2019 and 2021.
She reached her first final since 2022 in Auckland eight days ago, only to retire injured.
“I’ve been practising pretty well… so it seems to be going good,” she said.