Wimbledon champion Garbine Muguruza struggled with the heat and Hsieh Su-wei's game before losing 7-6 (1), 6-4 (4) as the upsets intensified at the Australian Open.
No3-ranked Muguruza follows Venus Williams and US Open champion Sloane Stephens out of the tournament in the first week, leaving only three major winners still in the women's draw — and two of them could meet in the third round.
Muguruza had five double-faults, including one to give No88-ranked Hsieh a match point, and made 43 unforced errors. She needed a medical time out in the first set, and accidently hit a ball into a line judge in frustration.
Hsieh, 32, is a former top-ranked doubles player who had only one previous win over a top 10 player and whose career-high singles ranking peaked at 23 in 2013.
On a day of 39 degree heat, Maria Sharapova was in a hurry to get off the Rod Laver Arena court, winning the first set in 23 minutes before advancing 6-1 7-6 (4) over 14th seed Anastasija Sevastova.
Ninth-seeded Johanna Konta, the 2016 Australian Open semifinalist, went down to US lucky loser Bernarda Pera 6-4 7-5.
Six-time men's singles champion Novak Djokovic made it through to the third round after outlasting French opponent Gail Monfils.
Djokovic looked far from his best but was still too good for the enigmatic world No39, maintaining his perfect record against Monfils with a 4-6 6-3 6-1 6-3 victory.
ASB Classic finalist Juan Martin del Potro, of Argentina, beat Russian Karen Khachanov 6-4 7-6(4) 6-7(0) 6-4 in a 4-hour marathon to advance in the Hisense Arena torture chamber.
• New Zealander Marcus Daniell and British partner Dominic Inglot have progressed to the second round of the men's tennis doubles. The pair beat Canadian Adil Shamasdin and Britain's Neal Skupski 6-4 2-6 6-3.
However, another New Zealander, Michael Venus, and South African partner Raven Klaasen have been dumped out at the first hurdle. The eighth seeded pair were beaten 7-6 (16-14) 7-6 (4) by American Scott Lipsky and Spaniard David Marrero in a match which stretched to an hour and 43 minutes.