Emma Raducanu's US Open title defence ended at the first hurdle, while Wimbledon champion Elena Rybakina and twice US Open winner Naomi Osaka were also ousted in the opening round.
British teenager Raducanu made a dream run to the title as a qualifier last year but her return to court at Flushing Meadows was less memorable as she fell 6-3 6-3 to Frenchwoman Alize Cornet.
"Obviously really disappointing. Really sad to leave here. It's probably my favourite tournament," Raducanu said. "In a way I'm happy because it's a clean slate... The target will be off my back slightly."
Rybakina became the latest top seed to exit the tournament after suffering a shock 6-4 6-4 defeat by French qualifier Clara Burel while Osaka, unseeded this year, lost 7-6(5) 6-3 to Australian open finalist Danielle Collins.
World number one Iga Swiatek cruised into the second round after crushing Italy's Jasmine Paolini 6-3 6-0, but two-time U.S. Open winner Venus Williams bowed out after losing 6-1 7-6 to Alison van Uytvanck of Belgium.
Rafael Nadal, returning to Flushing Meadows for the first time since winning the 2019 title, overcame an early scare to see off 21-year-old Australian wildcard Rinky Hijikata 4-6 6-2 6-3 6-3.
Third seed Carlos Alcaraz, who became the youngest man to reach the quarter-final in New York a year ago, advanced after his Argentine opponent Sebastian Baez retired when the Spanish teenager was leading 7-5 7-5 2-0.
- Reuters