Stefanos Tsitsipas battled into the Australian Open's last eight on Sunday but women's top seed Iga Swiatek and a tearful Coco Gauff became the latest big-name victims.
Swiatek's defeat to Elena Rybakina made it the first Grand Slam since the Open era began in 1968 to lose the top two seeds in both the men's and women's draws before the quarter-finals.
Tsitsipas, who is pursuing a first major crown, defeated the Italian 15th seed 6-4, 6-4, 3-6, 4-6, 6-3 to set up a quarter-final with the unseeded Jiri Lehecka.
"It was a long match, I felt like I spent an entire century on this court playing tennis," said the 24-year-old Tsitsipas, who has seen the draw open up for him with six of the top 10 seeds out.
Czech world number 71 Lehecka defeated sixth seed Felix Auger-Aliassime in four sets in yet another surprise result.
The 21-year-old Lehecka was knocked out in the first round at the four majors last year but was too hot for the Canadian, winning 4-6, 6-3, 7-6 (7/2), 7-6 (7/3).
Giant-killer Sebastian Korda surged into a maiden Grand Slam quarter-final and faces 18th-seeded Karen Khachanov of Russia.
Wimbledon champion Rybakina swept past the 2022 French and US Open winner Swiatek 6-4, 6-4 in 1hr 29min at a stunned Rod Laver Arena.