The first match takes place at 5pm Irish time.
The US Open semi-final line-up will be completed later.
Serena Williams goes up against the unseeded Tsvetana Pironkova, the Bulgarian hadn't played a professional match in over three-years prior to last week.
Meanwhile, last year's beaten finalist Viktoria Azarenka plays Elise Mertens.
Men's third seed Daniil Medvedev faces fellow Russian Andrey Rublev.
And second seed Dominic Thiem locks horns with Alex De Minaur.
Last night, Alexander Zverev became the first man to cement his place in the last four, the German fifth seed came from a set down to beat Borna Coric in New York.
He'll face Pablo Carreno Busta in the last four after the Spaniard beat Denis Shapovalov in five sets.
In the women's draw, Naomi Osaka cruised through to the semis with victory over Shelby Rogers.
She'll next play American Jennifer Brady, who beat Yulia Putintseva.