Polish fourth seed Agnieszka Radwanska was knocked out of the US Open on Wednesday, going down 6-3, 6-4 to China's Peng Shuai in the second round.
Radwanska, the champion in Montreal in the run-up to the tournament, had also lost to the Chinese player at the same stage in New York in 2010.
Her defeat continued her miserable record at the US Open where she has never got beyond the fourth round.
Peng, the world number 39 who made the fourth round in 2011, goes on to face either Roberta Vinci of Italy or Irina-Camelia Begu for a place in the last 16.
Meanwhile, five-time champions Roger Federer and Serena Williams reached the second round on Tuesday, but found themselves sharing the headlines with teenage upstarts CiCi Bellis and Borna Coric.
Federer claimed his 50th win of 2014 as the 17-time major winner, playing in his 60th successive Grand Slam and bidding to become the oldest major winner in over 40 years, defeated Australia's Marinko Matosevic 6-3, 6-4, 7-6 (7/4) to register his 23rd win in 24 night matches in New York.
Women's world number one Williams, the double defending champion who is also seeking a sixth title, was equally untroubled, defeating 18-year-old compatriot Taylor Townsend, 6-3, 6-1 in just 55 minutes.
But on Tuesday Bellis, ranked at a lowly 1,208 and aged just 15, knocked out Australian Open runner-up, Dominika Cibulkova, the 12th seed, 6-1, 4-6, 6-4 to become the youngest player to win a match at the US Open since Anna Kournikova in 1996.
Coric also made a stunning Grand Slam debut with a convincing 6-4, 6-1, 6-2 win over 29th-seeded Czech Lukas Rosol, the man who dumped Rafael Nadal out of Wimbledon two years ago.
Wimbledon champion Petra Kvitova breezed into the second round with a 6-1, 6-0 rout of French number 73 Kristina Mladenovic.