The 25-year-old drew a raucous, socially distanced crowd to his favoured John Cain Arena and kept them highly entertained, with the atmosphere electric in a gripping clash with Frenchman Ugo Humbert.
He eventually came through 5-7, 6-4, 3-6, 7-6 (7/2), 6-4 after 3hrs 25mins against the 29th seed to set up a blockbuster clash with third seed Dominic Thiem.
"Honestly, I don't know how I did that. I don't even know what to say, I'm lost for words. That is one of the craziest matches I've ever played," Kyrgios said.
Kyrgios said he was spurred on by the atmosphere, described by court-side interviewer Jim Courier as the best at a tennis match since the pandemic.
"I haven't played for a year, he's (Humbert) been playing some great tennis last year. The one thing I probably have him on right now is experience," Kyrgios said. "I've just drawn from experience so much on this court, you know, playing in front of you guys (fans), coming back from two sets to love here.
"Just had so many experiences. I tried to draw and that and try and put my head down, try and make him play."
Left-hander Humbert, 22, was bidding to reach the third round of a Slam for only the second time, but he was no pushover, having won two Tour-level titles last year, at Auckland and Antwerp.
He served to love to open proceedings in front of the pro-Kyrgios crowd.
Playing to the crowd, the unseeded Australian unleashed an underarm serve to catch the Frenchman off guard and win the game for 2-2.
It didn't take long for more drama to unfold, with Kyrgios taking issue with the let machine after two questionable calls, demanding the umpire reset it.
"This high over the net," he gestured to the umpire. "Reset the machine, because the ball is this far off the net. Look at the replay."
Kyrgios, constantly muttering to himself, was unable to settle with Humbert returning well and getting under his skin.
He broke Kyrgios to take the first set with the Australian smashing his racquet in frustration.
But he quickly shook off the disappointment to break in the third game of the next set and hung on to level the match, again ranting about the let machine.
Humberg kept his cool and was unrelenting, with Kyrgios earning a warning for racquet abuse after being broken en route to losing the third set.
With the wheels coming off, Humberg broke immediately in the fourth set and looked on course for victory.
But Kyrgios saved two match points to break back and with the crowd roaring him on, he raced through the tiebreaker to take it to a fifth set, throwing in another underarm serve for good measure.
Fired up, he broke in the third game of the fifth and Humberg's resistance crumbled.