Angelique Kerber ended the 19-match win streak of Wimbledon and Olympic champion Serena Williams on Friday with a 6-4 6-4 victory in the quarter-finals of the Cincinnati Masters ATP/WTA event.
The German fifth seed double-faulted on one match point but concluded with a winning ace on another to send the second seed out of the event, one which Williams has never won.
Williams destroyed a racquet in a fit of anger during the loss but will now have the rest days she has been seeking during her summer of success ahead of the start of the US Open, which begins on August 27.
Kerber, a two-time grand slam semi-finalist, said that while she felt some nerves as she tried to close out Williams, her game withstood the big test.
"I was nervous at the end but I told myself to just keep hitting the ball," Kerber said. "Serena has been playing well. This was a good win for me and I'm very pleased."
It was the opposite story for elder Williams sister Venus, who upset defending US Open champion Samantha Stosur 6-2 6-7 (2-7) 6-4.
The 32-year-old American twice had to serve for victory in the final set, nailing it on her second attempt from 5-4 after two and a half hours.
Williams has won six of seven matches with Australian Stosur, who stands 4-5 record since a Roland Garros semi-final two months ago.
"It's always disappointing to lose when you play a good match like that and you think you've done enough almost to win," Stosur said. "Still, I had three really good matches here and can get confidence and gain a bit of momentum going into New York."
Men's reigning US Open champion Novak Djokovic has booked a semi-final date with Olympic bronze medallist Juan Martin del Potro by beating Marin Cilic.
Serb second seed Djokovic took only 80 minutes to dispatch the Croatian 6-3 6-2, improving to 7-0 in their career rivalry.
Argentine sixth seed Del Potro advanced to the rematch of the London Olympic bronze-medal match by ending the giant-killing run of Frenchman Jeremy Chardy 6-1 6-3.
Del Potro has won his past two matches against Djokovic, including the bronze showdown and in a Davis Cup tie last September.
"The match with Del Potro won't be for revenge," Djokovic said. "This is sport. You win and you lose. He is playing with confidence and it will be a big challenge to play him."
Djokovic is maintaining momentum after winning the Toronto Masters event last week. He advanced 6-0 on Thursday when injured Nikolay Davydenko retired and kept Cilic on the defensive in their quarter-final.
"It was a very good match, my best of the tournament," Djokovic said. "I'm on good form. I may have grown up on clay, but I've achieved my best career success on hardcourts."
Del Potro, who will travel to the Mayo Clinic next week to have his sore left wrist checked out by the same doctors who operated on his right wrist in 2010, has reached the last eight in seven of the nine ATP Masters 1000 events.