Second seed Simona Halep and two-time Wimbledon champion Petra Kvitova reached their first US Open quarter-finals while old-hands Victoria Azarenka and Flavia Pennetta also went through.
Halep overcame injury and 30-degree heat to set-up a last-eight clash against two-time runner-up Azarenka.
Halep needed 2hr 38 min, as well as a 10-minute heat break, to down German 24th seed Sabine Lisicki 6-7 (6/8), 7-5, 6-2.
Halep, 23, is the first Romanian in the last eight in New York since Irina Spirlea went to the 1997 semi-finals.
But she did it the hard way, letting two set points slip away in the first set before then requiring a medical timeout to have her left thigh tightly strapped.
There were 17 service breaks, nine of them in the second set, while both players committed a total of 105 unforced errors, 72 off the German's racquet.
"It's unbelievable to reach my first quarter-final at the US Open. It was a crazy match," said Halep after her fourth successive win over the 2013 Wimbledon runner-up.
"I'm pretty tired but I would have been very unhappy with myself had I lost."
Despite the injury, Halep insisted it was Lisicki who was the keener of the two to take advantage of the heat rule, which allows women players to leave the court for 10 minutes after the second set if the temperature goes beyond 30.1 degrees.
"She took the break so I went out too and cooled down."
Azarenka reached her fourth quarter-final in four years with a 6-3, 6-4 win over Varvara Lepchenko of the United States.
The former world number one, whose season has been stalled by a left thigh strain, appeared on Arthur Ashe Stadium with both biceps tightly strapped.
"It's a little embarrassing. I have blisters from my shirts rubbing against my arms so I needed the bandages," said Azarenka, the runner-up to Serena Williams in 2012 and 2013.
"It looks weird but I did what I have to do."
Azarenka, a two-time Australian Open champion, holds a 2-0 career lead over Halep, although their last meeting was back in 2012.
"I'm a different player since then. I'm stronger mentally. I'm stronger physically. Will be a new match," said Halep, the in-form hardcourt player this summer with runs to the finals in Toronto and Cincinnati.
Czech fifth seed and double Wimbledon champion Kvitova saw off British qualifier Johanna Konta 7-5, 6-3.
Kvitova is the first Czech in the quarter-finals since Daja Bedanova in 2001.
The 24-year-old Australian-born Konta had hoped to become the first British woman in the last-eight since Jo Durie in 1983 but she failed to take advantage of any of her five break points.
Kvitova will next face Italian 26th seed Pennetta, who reached her sixth quarter-final in seven years with a 6-4, 6-4 win over Australia's Samantha Stosur, the 2011 champion.
It was the 33-year-old Pennetta's seventh win in seven meetings against the 22nd seed.
"It was my best match of the year," said Pennetta after Stosur, the last woman to beat Serena Williams in New York, committed 35 unforced errors.
Pennetta has split her six meetings with Kvitova but has lost the last three, with her most recent win over the double Wimbledon champion coming in the Fed Cup in 2010.
Serena features on Tuesday when the quarter-finals get underway, facing sister Venus for the 27th time as she continues her bid to complete the calendar Grand Slam.
France's Kristina Mladenovic tackles fellow unseeded player Roberta Vinci, who reached the last-eight when Canada's Eugenie Bouchard pulled out with a concussion suffered in a locker room fall.
Source: AFP
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