Novak Djokovic crashed to his first defeat of the season and first in Australia for six years with a stunning 6-4, 6-4 loss to Alex de Minaur who gave Australia a 1-0 lead over Serbia in their United Cup quarter-final on Wednesday.
Djokovic was hampered by a right wrist problem in Serbia's victory over Czech Republic on Tuesday and the world number one had it worked on again by a trainer before De Minaur earned a late break and went on to clinch the opening set.
Australian Open champion Djokovic dropped serve yet again to hand De Minaur a 4-3 advantage in the second set and saved three match points later, but was unable to prevent the shock loss ahead of the year's first Grand Slam later this month.
Djokovic was on a 43-match winning run in Australia and preparing for a tilt at an 11th Melbourne Park title having last lost in the country to Chung Hyeon in the fourth round of the 2018 edition when he was plagued by an elbow issue.
"It's extremely special," world number 12 De Minaur said after the biggest win of his career. "Novak's an unbelievable competitor and what he's done for the sport is pretty special.
"It feels surreal, it feels amazing and I'm happy to do it here in Perth and in Australia.
"Ultimately when you go against Novak, you've just got to go out there, try and enjoy, back yourself and no matter what, keep fighting till the end. Today was my day. I'm happy I was able to get the win. This one definitely means a lot."
Top seeds Poland earlier beat China to reach the semi-finals of the 18-team event after the big-hitting Hubert Hurkacz eased past Zhang Zhizhen 6-3, 6-4 and Iga Swiatek fought back from 2-0 down in the first set to beat Zheng Qinwen 6-2, 6-3.
It was Swiatek's third straight singles victory in the event which the world number one is using to prepare for this month's Australian Open.
Caroline Garcia and Adrian Mannarino guided France into the quarter-finals with a victory over Italy. World number 20 Garcia beat Jasmine Paolini 6-4, 5-7, 6-4 after Mannarino beat Lorenzo Sonego 6-4, 6-4 in the Group D tie.
Greece took a 1-0 lead over Canada in Group B as Australian Open runner-up Stefanos Tsitsipas won his first singles match of the season by beating Steven Diez 6-2, 6-3.
The Australian Open runs from on January 14-28.