World No.2 Karolina Pliskova, fifth-ranked Elina Svitolina and sixth seed Belinda Bencic all joined 2019 champion Naomi Osaka and seven-time victor Serena Willams on the Open scrap heap with shock third-round exits.
Anastasia Pavlyuchenkova secured her first career victory in seven attempts over world No. 2 Karolina Pliskova on Saturday (Jan 25) as the Australian Open lost another high seed in the third round.
Pliskova was previously unbeaten in 2020, having won the season-opening Brisbane International and two earlier matches in Melbourne.
Russian Pavlyuchenkova battled to a 7-6 (7-4), 7-6 (7-3) win over the second-seeded Czech, who joined defending champion Naomi Osaka and 23-time Grand Slam victor Serena Williams in making third-round exits.
Second seed Pliskova acknowledged that while the Russian had played well her own performance was nowhere near what she is capable of.
"I love this game (tennis) and that's what drives me, I appreciate more what I have now", Pavlyuchenkova said. "Maybe not huge errors, but I did a lot", she said. I had goosebumps after some points.
The Czech levelled for 4-all but couldn't maintain momentum, squandering no less than five break opportunities that would have put her 6-5 ahead and in the lead for the first time.
German Angelique Kerber, seeded 17th, defeated Camila Giorgi 6-2 6-7 (4) 6-3 to improve her head-to-head record against the Italian to 5-0.
This seemed another big chance for the Czech, arguably the best player on the WTA Tour over the past three or four years, to win a first grand slam title.
The resurgent Muguruza plays ninth seed Kiki Bertens or Zarina Diyas next on Monday for a quarter-final spot.
Fourth seed Simona Halep, the beaten finalist two years ago, was impressive in a 6-1, 6-4 victory over Yulia Putintseva but another top-10 player was sent packing, sixth seed Belinda Bencic winning just one game in a 6-0, 6-1 defeat by Anett Kontaveit. "It's great to be in the second week in Melbourne again".