He was fit enough to play a shortened exhibition match against Novak Djokovic on Friday night, which he won.
A devasted Kyrgios said he had been feeling discomfort in his knee for the last fortnight and he “did not pull up great” after the hit and giggle with Djokovic.
“I’m devastated obviously, it’s my home tournament,” Kyrgios said.
“Barely had good night sleep last four or five nights, it’s just been throbbing.”
He called it “bad timing” but said, “injuries are part of the sport”.
Kyrgios doesn’t believe it’s a career-threatening injury but said he will draw inspiration from Thanasi who has bounced back from multiple injuries and has no doubt he’ll be back “to full strength” and playing his best tennis.
Kyrgios has been due to face Roman Safiullin in the first round on John Cain Arena on Tuesday night.
Had he progressed through the first week of the tournament, a mouthwatering match-up with Novak Djokovic awaited in the quarterfinals.
Kyrgios had also been set to reunite with Kokkinakis in a bid to defend their Australian Open doubles title.
But all of those possibilities are out the window not the Australian Open’s biggest drawcard is out of the tournament.
It’s a huge blow to the grand slam, which was banking on Kyrgios making a deep run as Australia’s top hope in the absence of the retired Ash Barty.
Kyrgios joins World No 1 Carlos Alcaraz as high-profile players who won’t be playing at Melbourne Park this year.
His withdrawal means Australia enters its home grand slam without its top-ranked male and female player.
Ajla Tomljanovic pulled out of the Australian Open on Saturday, explaining she hadn’t recovered from a left knee injury in time.
The women’s singles draw is also missing two-time champion Naomi Osaka, Venus Williams and Paula Badosa.