Venus Williams’ 24th US Open was brought to an abrupt end inside Arthur Ashe Stadium on Tuesday night.
The two-time winner, handed a wild card at the age of 43, was beaten 6-1 6-1 in the first round by Belgian Greet Minnen.
The American said: “I have to give credit to my opponent, there wasn’t a shot she couldn’t make.
“I don’t think I played badly, it was just one of those days where I was unlucky.
“I was really happy to be here. I love playing here and I really gave it my all today.”
Wimbledon runner-up Ons Jabeur had to overcome breathing difficulties to battle past Columbia’s Camila Osorio.
The Tunisian had her blood pressure checked at one point before securing a 7-5 7-6 (4) victory.
France’s Caroline Garcia, seeded seven, suffered a shock exit, 6-4 6-1, to world number 114 Wang Yafan of China.
Canadian Laylah Fernandez, the runner-up to Emma Raducanu two years ago, lost in three sets to Ekaterina Alexandrova.