World number one Simona Halep became the first top-seeded woman to lose in the US Open first round, falling to a 6-2 6-4 defeat against Kaia Kanepi.
The 26-year-old Romanian's serve was broken five times in the first match on the new Louis Armstrong Stadium.
She fought back from a double break down to 4-4 in the second set but the Estonian broke again before Halep sent a forehand long on match point.
Halep also lost her opening match at Flushing Meadows last year.
The French Open champion was beaten by Maria Sharapova in New York in 2017.
Halep, who reached the 2015 semi-finals and the last eight in 2016, said the intense surroundings could be an explanation behind her recent poor form at Flushing Meadows.
She said: "Maybe the noise in the crowd, the city is busy. So everything together. I'm a quiet person, so maybe I like the smaller places.
"But I had some great results here. I'm not complaining.
"I just say that I don't really feel 100% on my game when I step on the court here.
"Maybe in the future, it's going to change something, I will change something and it will be better."
Before Monday's defeat, no women's top seed had lost in the opening round at the US Open since the professional era began in 1968, the same year that the tournament was given its current name, having previously been known as the US National Championships.
World number 44 Kanepi, 33, reached the quarter-finals at Flushing Meadows last year but has had a succession of injury problems in recent years.
In contrast to Halep, the Estonian said she "loves" being in New York.
"I think the courts suit my game," she added. "I like the atmosphere at the tournament and in the city.
"And I like the weather: hot and humid."