The pair have been awarded a wildcard for the tournament, the US Tennis Association announced.
The New York event will be Williams' first appearance at the US Open since 2022. The 23-time Grand Slam singles winner made her comeback to the tennis court earlier this summer.
Spanish world number two Alcaraz announced earlier this week that he is set to defend his US Open singles title, after being out for four months due to injury.
The main mixed doubles tournament starts on Tuesday.
