Australia's Daria Saville upset top-seeded defending champion Jessica Pegula 7-5, 6-4 on Wednesday at the ATP and WTA Washington Open, where Hubert Hurkacz and Simona Halep also exited.
World number 88 Saville ripped the seventh-ranked American in hot and humid conditions while Romanian third seed Halep retired with illness down 7-5, 2-0 to Anna Kalinskaya.
"I stayed really composed," Saville said. "I managed the energy really well. It was very hot. But I thought it's hot for everyone so get on with it."
Polish second seed Hurkacz crashed out in his second-round match at the US Open hardcourt tuneup, falling to Finland's Emil Ruusuvuori 6-4, 7-6 (7/3).
Wimbledon runner-up Nick Kyrgios of Australia defeated US 14th seed Tommy Paul 6-3, 6-4 to book a third-round date with US fourth seed Reilly Opelka.
World number 63 Kyrgios, whose most recent title came at Washington in 2019, broke to open and close the first set. Paul's fourth double fault gave the Aussie a match point and his forehand shot beyond the baseline gave Kyrgios the victory in 85 minutes.
Saville booked a quarter-final match against Canadian qualifier Rebecca Marino, who beat Germany's Andrea Petkovic 6-3, 3-6, 6-1.
The 28-year-old Russian-born Aussie won her only WTA title at the 2017 Connecticut Open but dispatched Pegula in 98 minutes for her second top-10 win of the year after downing Ons Jabeur at Indian Wells in March.
"Everyone's attitude is I'm here to win the tournament and I'm no different," Saville said. "I'm playing really good tennis right now. I'm excited for more."
Saville fell to 627th in the world rankings after Achilles tendon surgery that sidelined her for most of last year. Now she's into her third quarter-final of the year after Miami and Guadalajara.
"I'm happy," Saville said. "It creates good reputation. Players are going to say, 'She's playing well. She has some good wins this year.'"
Ruusuvuori, set to rise one shy of his career-high to 43rd in the world rankings, denied Hurkacz on all four break-point chances to advance after one hour and 44 minutes.
"I just tried to hang in there and stay as tough as can," Ruusuvuori said. "Long rallies, they really drain you and you start to feel dizzy during the points. Very tough."
His third-round foe will be Sweden's Mikael Ymer, who ousted 15th seed Aslan Karatsev 6-4, 3-6, 6-4 after eliminating three-time Grand Slam champion Andy Murray in round one.
Japan's Yoshihito Nishioka ousted Aussie 11th seed Alex De Minaur 3-6, 7-6 (8/6), 6-2. The world number 96 will next face seventh seed Karen Khachanov.
US third seed Taylor Fritz beat Australia's Alexei Popyrin 6-4, 6-3 to book a third-round match against British 16th seed Daniel Evans.
World number 13 Fritz comes off a five-set Wimbledon quarter-final loss to Rafael Nadal and two weeks in a boot with a stress fracture in his left foot.