Seven-time Grand Slam winner Williams, 46, was eliminated in the first round at Flushing Meadows last year after falling to Czech Karolina Muchova.
She and sister Serena also returned to doubles action for the first time since 2022 on Monday, suffering an opening round defeat at the Cincinnati Open.
Sloane Stephens, the 2017 US Open winner, was also among those granted a wildcard on Monday. The 33-year-old is trying to make a comeback after a foot injury derailed her 2025 season.
Organisers said one women's singles wildcard spot is still to be announced.
On the men's side, Frenchman Gael Monfils was among those who got a wildcard into the main draw earlier this month. The former world number six previously announced that he would retire at the end of the season.
Monfils and spouse Elina Svitolina were also given wildcards into the US Open mixed doubles tournament on Monday.