Former Australian Open champion Stan Wawrinka won a five-set thriller to reach the quarter-finals while Alexander Zverev and Dominic Thiem both breezed through.
Wawrinka won his 300th tour-level match with a five-set victory over fourth-seeded Daniil Medvedev, who became the highest-ranked player to exit the men's draw.
The 2014 champion here dominated the fourth-set tie-breaker and then broke Medvedev in the opening game of the deciding set before going on to win 6-2 2-6 4-6 7-6 (7-2) 6-2.
Wawrinka is working his way back to the top after knee surgery in 2017 and he reached his third quarter-final at the last four Grand Slams with a stunning victory over the US Open finalist.
Medvedev had been tipped as the most likely challenger to the big three here after pushing Rafael Nadal to five sets in New York.
The Swiss will play seventh seed Alexander Zverev next after the German continued his brilliant run at the tournament by beating Andrey Rublev 6-4 6-4 6-4.
Zverev, who has promised to donate all his prize money to the wild fire relief efforts if he wins the title, arrived in Melbourne having lost all three matches at the ATP Cup and with his serve apparently in crisis but he has turned things round superbly.
The result, meanwhile, marked the end of Rublev's 15-match winning run taking in the Davis Cup finals and ATP Tour titles in Doha and Adelaide.
Austrian Thiem, twice a finalist at the French Open, had fallen at the fourth-round stage twice before but a repeat never looked on the cards this time as the fifth seed reached his first Australian Open quarter-final with a 6-2 6-4 6-4 victory over Gael Monfils.
"I think that I played my best match so far of this Australian Open. A very, very good feeling," the Austrian said.
"The score looks way easier than the match was. I think I was lucky to make an early break in each set and then was managing to hold my serve well. I'm so happy because I'm for the first time in the quarter-finals here."
Thiem's mother began a tradition last year of getting a tattoo every time he captures a title and the world No 5 was asked about it after his win.
"Unfortunately I have to confirm it," Thiem, who won five titles last year, said in a court-side interview to leave the crowd in stitches. "I really would like to deny it, but no."
Asked what she could get inked if he clinches the title by winning his next three matches in Melbourne, Thiem said: "For sure, a kangaroo."
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