The only Grand Slam champions left in the women’s draw will meet when Venus Williams plays Petra Kvitova in the US Open quarter-finals on day nine.
American ninth seed Williams and Czech 13th seed Kvitova open the night session at 00:00 BST on Wednesday.
Williams is the only former US Open winner in the last eight and looking for her first major win in nine years.
“I’ll take any advantage I can get, let’s face it,” said the 37-year-old, who was champion in 2000 and 2001.
“But at the end of the day when I go out there and someone’s across the net from me, they’re playing well. They’re not going to give you any matches.”
The pair will be followed onto Arthur Ashe Stadium by American 17th seed Sam Querrey and 28th seed Kevin Anderson of South Africa.
Williams has reached the finals at the Australian Open and Wimbledon this year, and is in contention to win a third US Open 20 years after making the final on her debut.
The seven-time major champion has overcome injuries and illness in recent years, while Kvitova faces a Grand Slam quarter-final nine months after suffering a knife attack.
The Czech, 27, required surgery on her playing hand and only returned to the sport in May.
“What she’s gone through is unimaginable, unreasonable. The world we live in is just shocking,” added Williams.
“So for her, I think to be playing well is such a blessing. To be able to come out here and do what she needs to do, to clear her head, it’s such a beautiful thing to see.”
Kvitova, who leads their head-to-head record 4-1, said: “We always had tough battles but I will try my best.
“She’s a big server of course. She has something special which the other players doesn’t have.”
Spanish 12th seed Pablo Carreno Busta and Argentina’s Diego Schwartzman, the 29th seed, open play on Ashe at 17:00 on Tuesday.
Unseeded American Sloane Stephens then takes on Latvian 16th seed Anastasia Sevastova, who overcame Maria Sharapova to reach the last eight.