Men's top seed Carlos Alcaraz will play unseeded Australian Adam Walton in the Spaniard's quest for a first title in Melbourne to become the youngest man to complete the career Grand Slam.
At the draw ceremony at Melbourne Park on Thursday, 10-times champion Novak Djokovic, the fourth seed, was bracketed next to 71st-ranked Spaniard Pedro Martinez.
Serb Djokovic, who is gunning for an all-time record 25th Grand Slam title to break clear of a tie with Margaret Court, could face rising Italian Lorenzo Musetti, the fifth seed, in the quarter-finals before a possible semi-final against Sinner.
Italian Sinner has a smooth first week but fans will hope it includes a third round match-up with 28th-seeded Brazilian Joao Fonseca should the exciting, 19-year-old talent prove fit following recent back problems.
“The draw is very difficult, it doesn’t matter who you play," said Sinner at the draw ceremony. "We are the best players in the world and the way is very, very long."
Alcaraz has home hero Alex de Minaur in his quarter of the draw but the Australian sixth seed must pass a tricky first test against Italian Matteo Berrettini, the Wimbledon runner-up in 2021.
Twice champion Sabalenka has few threats in her quarter of the draw before a potential semi-final against third seed Coco Gauff, who opens against 55th-ranked Uzbek Kamilla Rakhimova.
Women's second seed Iga Swiatek will meet a qualifier in the first round but her path to a first Australian Open title and seventh Grand Slam crown overall could mean a crunch quarter-final against the resurgent Kazakh Elena Rybakina.
Former Wimbledon champion Rybakina, the fifth seed, looms as a dangerous proposition after clinching her maiden WTA Finals trophy in November in a major return to form.
Rybakina meets unseeded Slovene Kaja Juvan in the first round.
Defending champion Madison Keys will face unseeded Ukrainian Oleksandra Oliynykova but the American ninth seed has a tough road to the title.
Keys could meet sixth-seeded compatriot Jessica Pegula in the fourth round before a potential quarter-final against another American in fourth seed Amanda Anisimova.
Home favourite Thanasi Kokkinakis, who had a protected ranking for the Australian Open due to injury, pulled out of the men's draw on Thursday after suffering a shoulder injury at the Adelaide International.