Williams and Alcaraz have been drawn to face one of the teams that advances from the eight-team qualifying tournament that will be played on Monday.
Williams will be returning to the US Open for the first time since 2022. The six-time singles champion and Alcaraz, who has won the men's title twice, were awarded a wildcard into the 16-team mixed tournament on Saturday.
The first round and quarter-finals of the mixed doubles are Tuesday, with the semi-finals and final on Wednesday. The winning team shares $US1 million ($A1. 4 million).
Facing one of the qualifiers will be a tough assignment because most of the players in the qualifying tournament are doubles specialists.
The qualifying tournament was added this year to give those types of players a chance to compete after they were almost entirely shut out last year when the US Tennis Association, seeking more star power, revamped the mixed doubles and based direct entry on the players' rankings in singles.
Two-time defending women's champion Aryna Sabalenka and 23-time grand slam singles champion Novak Djokovic are the No.1 seeds after having the lowest combined singles ranking among the teams. They will face the pair of Leylah Fernandez and Frances Tiafoe in their first match.
Americans Jessica Pegula and Taylor Fritz are seeded second and will open against Diana Shnaider and Casper Ruud. Ruud was scheduled to play again with Iga Swiatek, after they reached the final in 2025. But Swiatek withdrew and Schnaider needed a partner after Daniil Medvedev pulled out.
The other first-round matches include married pair Elina Svitolina and Gael Monfils against Alex Eala and Felix Auger-Aliassime and Belinda Bencic and Flavio Cobolli versus Taylor Townsend and Alexander Zverev.
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