Serena is on course to claim the 22nd major title of her career, which would also be a record seventh US Open crown and her fourth in succession, while victory would also see the 33-year-old claim the first calendar grand slam since Steffi Graf in 1988.
World No1 Serena has racked up 32 wins at major events since losing to France’s Alize Cornet at Wimbledon last year, although standing in her way is Venus, who is set to feature in the last eight at Flushing Meadows for the first time since 2010.
“No-one is out to be a spoiler, but at the same time you’re focused on winning your match,” said Venus.
Serena has won six of the last seven battles against Venus, with the latest a straight-sets triumph on Centre Court at Wimbledon this year, and she leads the overall head-to-head tussles 15-11.
“I’m playing, for me, the best player in the tournament, and that’s never easy,” said Serena. “She’s beaten me so many times. I’ve taken a lot of losses off of her – more than anybody.
“She’s a player who knows how to win, knows how to beat me, and knows my weaknesses better than anyone.”
French Open winner Stan Wawrinka, meanwhile, sealed his quarter-final place with a a 6-1, 1-6, 6-3, 6-4 victory over American Donald Young, who had knocked out Slovenia-born Briton Aljaz Bedene in round two of the competition.
There were unfortunate scenes as Britain’s top junior Katie Swan, an Australian Open junior finalist, had to be helped from court six in some distress after receiving medical attention for around 10 minutes.
The Birstol-born 16-year-old, who had only just returned from injury, lost the first set in soaring temperatures to France’s Tessah Andrianjafitrimo and, despite wanting to carry, was unable to when trailing 7-6 (7-5), 3-0.