The pair survived three match points in a brilliant fightback on Friday night, prevailing 6-7 (6-8) 6-4 12-10 over Desirae Krawczyk and Neal Skupski.
Kyrgios was too banged up to compete in the singles tournament and was punted from the men's doubles with good mate Thanasi Kokkinakis the previous night.
But despite sporting bandages on both knees, the 30-year-old showman was in his element alongside Fernandez in front of a boisterous crowd at ANZ Arena.
"That was some of the most craziest energy that I've had," Kyrgios said afterwards.
"I've obviously played some amazing matches at the AO but that's got to be one of my favourite ones.
"(We were) 9-6 down, 7-3. Realistically, tennis players don't always believe you can come back.
"But I was like, 'If we just went one at a time, maybe we can do it.'
"The crowd were amazing all day. They stayed, they hung around and it was amazing. I'm really excited for our next round."
Both grand slam singles finalists, Kyrgios and Fernandez can continue to dream of a major mixed doubles title at Melbourne Park.
They will face either British pair Olivia Nicholls and Henry Patten or Anna Danilina and JJ Tracy in the second round.
Canadian Fernandez credited Kyrgios' positive energy for keeping the pair in their first-round match.
"I felt like Nick was the most positive guy there," Fernandez said.
"It was so cool, it was just a lot of fun. Nick brought the great energy and also the crowd."
The result derailed American Krawczyk's bid for a career grand slam in mixed doubles.
The 32-year-old won each of the other three major mixed doubles titles in 2021, and backed up at Wimbledon the following year.
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