New York - Lucie Safarova joined the US Open seeds casualty list on Tuesday when the Czech left-hander became the fourth top-10 player to lose in the first round.
Sixth-seeded Safarova slipped to a 6-4, 6-1 defeat to Ukraine's Lesia Tsurenko, the woman she defeated in the semi-finals in New Haven just last week.
"I talked with my coach about what to change. I changed the serve a little bit, made it a more active movement," said the 26-year-old Tsurenko of the tweaks she made from last week's clash with the Czech, who had also beaten her in New York in 2013.
"I received pretty bad because she was a lefty. This time I was playing at the back more."
Safarova, the French Open runner-up, joins seventh seed Ana Ivanovic, eighth-ranked Karolina Pliskova and Carla Suarez Navarro, the 10th seed, in failing to get out of the first round.
With world number three Maria Sharapova having pulled out of the tournament through injury, Safarova's defeat also served to ease Serena Williams's path to a calender Grand Slam.
The world number one reached the second round on Monday when Vitalia Diatchenko retired with a foot injury after just 30 minutes.
World number two Simona Halep avoided the upsets when she reached the second round thanks to New Zealand opponent Marina Erakovic retiring with a knee injury.
Halep was leading 6-2, 3-0 when her 99th-ranked rival called it quits, having received a medical timeout for treatment on her right knee at the end of the first set.
Romanian 23-year-old Halep goes on to face either Kateryna Bondarenko of Ukraine or Yulia Putintseva of Kazakhstan for a place in the last 32.
"I had a good start. I was aggressive and played my best tennis today," said Halep who has yet to get beyond the fourth round in New York.
"I know I can play my best tennis here. I have no expectations. Serena is there. I just want to play my best tennis."
Another early winner on Tuesday was German 11th seed Angelique Kerber, a 2011 semi-finalist, who saw off Romania's Alexandra Dulgheru 6-3, 6-1.
Later Tuesday, five-time champion Roger Federer gets his bid to become the oldest US Open winner in 45 years underway.
But he is likely to be overshadowed by Andy Murray's clash with enfant terrible Nick Kyrgios.
Federer, the second seed who won five years in succession at Flushing Meadows from 2004-2008, starts against Leonardo Mayer, the 34th-ranked Argentine.
The 34-year-old Federer won the pair's only other meeting in Shanghai last year but had to save five match points in the process.
Federer has not been back to a US Open final since losing the 2009 title match to Juan Martin del Potro and was a semi-final loser in 2014.
But he made the Wimbledon final again in July and a victory over Novak Djokovic in the Cincinnati Masters final last month served to boost his belief that he can add to his 17 majors, the last of which came at the All England Club in 2012.
Murray, the 2012 champion, begins his campaign against controversial Australian Kyrgios, the world number 37.
Kyrgios is playing under the shadow of a suspension following his now-infamous, lurid tirade against Stan Wawrinka in Montreal.
Kyrgios was picked up by courtside microphones claiming that compatriot Thanasi Kokkinakis had slept with WTA player Donna Vekic, the girlfriend of Wawrinka.
The Australian was widely condemned for the outburst but Murray has pleaded for patience.
"He's a young guy. He made a mistake. All the guys here when they were 19 or 20 made mistakes. His was seen by millions. It's unfortunate it happened. It was wrong," said Murray of his 20-year-old opponent who he has defeated three times in three meetings.
Wawrinka, the fifth seed who made the semi-finals in 2013, starts against Spain's Albert Ramos-Vinolas.
Also in action are former women's runners-up Caroline Wozniacki and Victoria Azarenka.
Fourth seed Wozniacki faces US college champion Jamie Loeb while Azarenka tackles Lucie Hradecka of the Czech Republic.
Two-time Wimbledon champion Petra Kvitova, seeded fifth, plays Germany's Laura Siegemund.