Venus has fared better in doubles in recent years, reaching the quarter-finals in New York last year alongside Canada’s Leylah Fernandez.
She has not won a singles match at a Grand Slam since Wimbledon in 2021, where she reached the second round.
However, the Williams sisters still draw huge crowds together or separately, with stands packed out in Cincinnati for their recent return.
Serena, a 23-time Grand Slam singles champion, played what was expected to be the last tournament of her career in New York in 2022.
However, she made her return first in doubles at Queen’s in June before being given the final Wimbledon women’s singles wildcard.
Venus won her first US Open singles title in 2000, two months after earning her maiden major at Wimbledon.
She beat Serena in the final a year later to defend her title – the first of nine major showpieces the sister would contest.
Venus became the oldest US Open singles player in 44 years when she played at the tournament last year.
She lost in three sets to ninth seed Karolina Muchova and gave an emotional news conference afterwards, saying it was “nice to be free”.
In 2011, Williams was diagnosed with Sjogren’s syndrome, an incurable autoimmune disease with symptoms including pain, numbness and fatigue.
She spoke in 2025 about the impact of painful fibroids – abnormal growths that develop in the uterus – on her daily life.
In the men’s draw, France’s Gael Monfils has been awarded a wildcard in the final Grand Slam of his career.
The 39-year-old, who reached the New York semi-finals in 2016, will retire at the end of the season.
There is also one remaining wildcard for the men’s singles, which could go to 2016 champion Stan Wawrinka.
The Swiss is also calling time on his career at the end of the year.