Two all-American semi-finals will take place on day 11 of the US Open as Venus Williams plays Sloane Stephens and Coco Vandeweghe faces Madison Keys.
It is the first all-US last four line-up at the tournament since 1981.
Williams, the 2000 and 2001 champion, and Stephens will be first on the Arthur Ashe Stadium in New York at 00:00 BST.
Vandeweghe, seeded 20th, 15th seed Keys and unseeded Stephens are aiming to reach their first Grand Slam final.
Williams and Stephens both won final-set tie-breaks to reach this stage, against Petra Kvitova and Anastasija Sevastova respectively.
Vandeweghe overcame Karolina Pliskova in straight sets to join them, while Keys saw off unseeded Estonian Kaia Kanepi.
Ninth seed Williams, 37, is the oldest semi-finalist at any Grand Slam since Martina Navratilova at Wimbledon in 1994.
“It’s such a wonderful feeling, because you put in so much work to be able to succeed at these moments,” said Williams.
“It has been a great two weeks for American tennis, seeing all the American players in the draw and all of them advancing so deep and competing so well.”
Stephens, 24, added: “Making the semi-finals of a Slam is a complete neutraliser, anybody’s game. I just have to focus on myself.
“Venus is just our leader, everyone looks up to her. She’s a great player, a great person. She’s a great leader.”
Arthur Ashe became the first black man to win a Grand Slam when he triumphed at the 1968 US Open and Williams and Stephens will face each other on the court named after the three-time major winner.
“It’s great for American tennis,” said Stephens. “It’s great for African-American women. I hope that we keep it going.”
Williams, who reached the final at her first US Open in 1997, the same year the Arthur Ashe Stadium made its debut, added: “He’s a total legend.
“He played during a time where he couldn’t just focus on the tennis. I’m very blessed to be able to focus on my game. But he had to fight because of the colour of his skin.
“It was a completely different time. So I can’t even imagine the pressure he was under. To come out of it with grace, as a champion, it’s incredible.”