It will be Williams' first competitive match at the US Open since 2022. The American 23-time Grand Slam singles champion and six-time US Open winner won the mixed doubles title in 1998 with Max Mirnyi.
World number one Aryna Sabalenka will partner Serbia's Novak Djokovic and Jessica Pegula will team up with fellow American Taylor Fritz in the mixed doubles.
Williams returned to doubles action this month alongside her sister Venus at the Cincinnati Open, but the pair lost in the opening round in their first tournament together since 2022.
The 44-year-old Serena announced her return to competitive tennis in June after a four-year absence.
