Top-ranked defending champion Naomi Osaka was ousted from the US Open on Monday by Belinda Bencic while Croatian Donna Vekic survived a match point to join the Swiss 13th seed in a quarter-final match-up.
Bencic's 7-5, 6-4 triumph, her WTA-best sixth over a top-five foe this year, ensured 21-year-old Japanese star Osaka will fall from atop the rankings next week and won't become the first repeat US Open winner since Serena Williams in 2014.
"The challenge cannot be bigger against Naomi," Bencic said. "I had to be at the top of my game and I'm really pleased how well I handled my nerves at the end."
Bencic, 22, matched her deepest grand slam run from the 2014 US Open with her third victory of the year over Osaka, having also won at Indian Wells and Madrid.
"She played pretty clean. She had a specific plan she wanted to execute," Osaka said. "I guess just being aggressive."
Australia's Ashleigh Barty, the reigning French Open champion, will move atop the rankings next Monday after the loss by Osaka, who defends her Australian Open title in January.
"I can look at this and be very disappointed and mad, but I'm not mad about it," Osaka said. "I'd like to reach higher rounds. That's definitely what I'll aim for in Australia."
Osaka's exit means there will be four different women's grand slam winners in a season for the third consecutive year, a first in the Open era.
Vekic, the 23rd seed, saved a match point in the second set and made her first Slam quarter-final by rallying past German 26th seed Julia Goerges 6-7, 7-5, 6-3.
"I don't even know how I won this match," Vekic said. "She was serving for the match. She had match point. I just kept fighting and believing I could win. It feels pretty amazing."
Bencic owns a 2-1 career edge over Vekic from two 2014 wins but Vekic won the most recent meeting with her friend and frequent practice partner in this year's French Open third round.
Belgian 25th seed Elise Mertens cruised past 141st-ranked US wildcard Kristie Ahn 6-1, 6-1 in 67 minutes to book a quarter-final berth against 19-year-old Canadian 15th seed Bianca Andreescu.
"I just tried to play my best game," said Mertens, who has dropped only 16 games in four matches.
"I try to improve every time. I try to invest in my game. It's coming out this week and hopefully I can go much further than this."
The only deeper slam run for Mertens was into last year's Australian Open semi-finals while Andreescu, whom the Belgian has never faced, extended her career-best slam performance by defeating 116th-ranked US qualifier Taylor Townsend 6-1, 4-6, 6-2.
Andreescu, a champion this year at Indian Wells and Toronto who could crack the world top 10 next week, improved to 6-0 this year against left-handers.
"It wasn't easy," Andreescu said. "I made sure to work on my passing shots during practice and it worked in the first and third sets. I'm glad I kept my cool at the end."
Andreescu breezed through the first set in 31 minutes, but double faulted to surrender the second set. She broke Townsend to open the third set and again for a 4-1 edge on the way to victory.
It's the first time all eight US Open quarter-finalists have been seeds since 2012 and a first at any Slam since the 2014 Australian Open.
Osaka took a pain-killer to ease nagging knee issues but nothing could help her overcome Bencic.
"I didn't move well. I was always flat-footed. She was aggressive," Osaka said. "The knee was a little bit annoying in the movement aspect but that was something I should have overcome."
