Vera Zvonareva, the second-seeded Russian, reached the third round yesterday with a three-set victory over 69th-ranked Kateryna Bondarenko of Ukraine.
Zvonareva, beaten by Kim Clijsters in the final at Flushing Meadows last year, survived 46 unforced errors to emerge with a 7-5, 3-6, 6-3 victory.
After dropping the second set, Zvonareva bore down to take a 4-1 lead in the third. Bondarenko broke back to narrow the gap to 4-3, but Zvonareva immediately recovered the break to serve for the match at 5-3.
She needed three match points to put away the tenacious Ukrainian, and had to fend off one last break point along the way. Zvonareva, whose two WTA titles this season took her career tally to 12, next faces Spain's 30th seed Anabel Medina Garrigues, who beat British qualifier Laura Robson 6-2, 6-3.
Among the men, the 10th-seeded Nicolas Almagro of Spain lost 6-2, 6-4, 6-3 to 81st-ranked and wild card entrant, Julien Benneteau of France.
Juan Martin del Potro, returning to the US Open for the first time since he won the 2009 title, faced Filippo Volandri later in the day.
Del Potro, seeded 18th, was unable to defend his title last year as he recovered from a wrist injury that sidelined him from January to September of 2010.
This season the Argentine has been steadily rebuilding his ranking, winning titles at Delray Beach and Estoril and reaching the semi-finals in three other tournaments.
Sixth-seeded Robin Soderling of Sweden withdrew with a viral illness yesterday.
Lucky loser Rogerio Dutra Da Silva took his place in the draw and defeated Louk Sorensen when the Irish qualifier retired while trailing in their match.
The local fans had plenty of home hopes to cheer for with eight American men in action. They included Andy Roddick, who was to face compatriot Michael Russell for a second-round berth, and big-serving John Isner, who was to face Cypriot Marcos Baghdatis.
Two former women's champions, Maria Sharapova and Venus Williams, were seeking third round berths.
Williams, unseeded at Flushing Meadows for the first time since her debut in 1997, faced big-serving German Sabine Lisicki, a Wimbledon semi-finalist.
Serena, Venus's sister, who is ranked 28th but still regarded a tournament favourite, had returned on Tuesday to the scene of her infamous rant with a lineswoman over a footcall that cost her a point penalty, and defeat to Kim Clijsters. She swatted aside Serbia's Bojana Jovanovski 6-1, 6-1.
Third-seeded Sharapova, who clawed her way past British teenager Heather Watson to reach the second round, took on Anastasiya Yakimova of Belarus.
Madison Keys, the American teenager, showed her inexperience late in her second-ever match at a grand slam tournament, repeatedly blowing leads in a loss to 27th-seeded Lucie Safarova. The 24-year-old Safarova won 3-6, 7-5, 6-4 yesterday to reach the third round. The 16-year-old Keys was the youngest player since 2005 to win a match at Flushing Meadows.