Australian Open champion and world number one Angelique Kerber followed men's top seed Andy Murray out of the competition in the fourth round after being stunned in straight sets by Coco Vandeweghe.
The form book has gone out of the window at Melbourne Park this year with Novak Djokovic, Agnieszka Radwanska and Simona Halep also licking their wounds after early defeats.
And Vandeweghe put her name alongside the likes of Denis Istomin and Mischa Zverev in earning an odds-denying victory, seeing off Kerber 6-2 6-3.
Venus Williams and Garbine Muguruza could be the biggest winners from Kerber's defeat as the top half of the draw opens up for the pair.
COCO POPS KERBER'S BUBBLE
In eight previous matches against top-four ranked opposition, Vandeweghe had only ever won once - against Radwanska in Birmingham last year - but she showed little regard for Kerber's lofty standing, attacking the German at every opportunity.
A career-best quarter-final run in this tournament represents just Vandeweghe's second venture into the second week of a major, but she earned it in style.
Winning four games on the bounce to take out the first set brought the lingering air of an upset back to Rod Laver Arena.
And Vandeweghe showed her ability to strike off the back foot in the second, dropping serve immediately but then winning four of the next six games, dropping only 11 points in that run to cap a display that appeared to be full of confidence, but the American said that was not necessarily the case.
"I guess if faked it a lot because I was feeling like crap out there! You just gotta keep out there and keep playing and hope for the best."
Vandeweghe's reward for victory is a meeting with seventh seed Muguruza, who is also into the quarter-finals of this tournament for the first time.
VENUS SYMPATHETIC BUT RUTHLESS
Williams has been imperious thus far and she secured a quarter-final spot with a fourth win without losing a set this week.
Mona Barthel had beaten Olympic champion Monica Puig on her way to a career-best show at a grand slam, but the seven-time major champion proved an obstacle too far, winning 6-3 7-5.
Barthel is on the comeback trail after her 2016 was punctured by health problems and Williams was sympathetic for her rival.
"I know what it's like to be down on your luck, but she knows how to play tennis and she's experienced," Williams said.
"We'd played a couple of tough matches before so today I expected to have some competition."
Anastasia Pavlyuchenkova (24) is next up for Venus after beating fellow Russian Svetlana Kuznetsova in straight sets to reach the Melbourne quarter-finals for the first time.
MUGURUZA ON TOP FORM AGAIN
Consistency has been the main drawback in Muguruza's career thus far. The Spaniard followed up her run to the 2015 Wimbledon final and winning last year's French Open with second-round exits at the next major.
In fact, last year Muguruza combined the Roland Garros title with first-week exits at each of the other slams.
But the 23-year-old has been in unerring form so far in this tournament, and Sorana Cirstea was no match for Muguruza, who picked up a 6-2 6-3 win to make the last eight without dropping a set.
"I am very happy. I went through the match very concentrated," Muguruza said.
"It was an important match. The last three years, I think I've lost in this round. It was the first time I go through. I'm in the quarter-finals."
Vandeweghe is evidently not to be underestimated, but a victory in their previous meeting in Cincinnati last year will give Muguruza confidence.