De Minaur carries the hopes of his expectant host nation at the tournament and represents their best shot at ending a 47-year wait for the first Australian men's singles champion at Melbourne Park since Mark Edmondson in 1976.
The Australian number one, who has been in fine form recently and dealt Djokovic a rare defeat in the United Cup, faces unseeded Arnaldi and is out for revenge after being part of the Australian squad that was beaten by Italy in the Davis Cup final last year.
"It's been shattering the last couple of years just to get so close to the Holy Grail and just barely miss out," De Minaur told reporters.
"I do associate Matteo as the guy that beat us in the Davis Cup final. I'll do my best to hopefully get some revenge. He's a quality opponent. I'll be ready for it hopefully...
"I said last year that it felt pretty special to play on Rod Laver on my own terms like I'm the one being scheduled, not because I'm playing Rafa (Nadal) or someone like that."
De Minaur's compatriot Popyrin has his work cut out for him as he takes on 10-time Australian Open champion Djokovic.
However, despite Popyrin having lost in straight sets in his only previous meeting with Djokovic at the Japan Open in 2019, the 43rd-ranked Australian said he was confident in his ability to cause the 24-time Grand Slam champion some problems.
"I don't think he's got any weaknesses...," Popyrin said.
"He is the greatest of all time in our sport, so to get there, you have to have no weaknesses. But I have big weapons in my game that I believe can do some damage."
In the women's draw, defending champion Aryna Sabalenka faces 16-year-old Czech Brenda Fruhvirtova, the younger sister of Linda, who made it to the fourth round of the Australian Open last year.
Top-10 seeds Coco Gauff, Barbora Krejcikova, Maria Sakkari and Beatriz Haddad-Maia are all in action, while former world number one Caroline Wozniacki faces Russian Maria Timofeeva.
