Three-time finalist Daniil Medvedev is also on a mission to safely negotiate the second round at Melbourne Park, as are third seeds Coco Gauff and Alexander Zverev.
Alcaraz started his bid for a career Grand Slam with a three-set defeat of home hope Adam Walton on Sunday and faces German Yannick Hanfmann.
He is the star attraction in the afternoon session on Rod Laver Arena, following Sabalenka onto the centre court.
The Belarusian takes on China’s Bai Zhuoxuan in her bid for a third Australian Open title in four years after dropping just five games in her tournament opener.
Spanish superstar Alcaraz already has six major titles aged 22, but success on the Melbourne Park hardcourts remains a glaring hole in his resume.
He has not made it past the quarter-finals in four trips to Australia.
“I just really want to perform better than I did previous years,” he said.
“So I just feel this year probably it is one of those years that I will be able to, or will have the chance, to go further.”
Sabalenka also has a point to prove after being upset by Madison Keys in last year’s final as the overwhelming favourite.
After winning the lead-up Brisbane International, she was in ominous form in her first-round clash, coming to the net 22 times as she adds more serve and volley to her repertoire.
“I think it’s very important to always be working on your game, always developing as a player, always searching for something that is new, that is going to help your game,” she said.
The unpredictable Medvedev, runner-up in 2021, 2022 and 2024, is trying to keep his emotions in check this year and will again be put to the test against Frenchman Quentin Halys on John Cain Arena.
Gauff takes on Venus Williams’ conqueror, Olga Danilovic of Serbia, after a straight-sets first-round win as she looks to better her best performance in Melbourne, which was a semi-final in 2024.
Zverev is in action in an evening match on John Cain Arena against France’s Alexandre Muller, the latest challenge in the German’s decade-long quest for a first Grand Slam title.
The world number three, runner-up last year to Jannik Sinner, dropped a set in his opening clash but said it was good to be stretched early in the tournament.
“It’s a positive for sure,” he said.
“Because you have been tested and you know where you are and you know where your level is at, especially in difficult moments.”
Home hopes dominate the evening action on Rod Laver Arena with sixth seed Alex De Minaur facing Serbia’s Hamad Medjedovic before Priscilla Hon meets American Iva Jovic.