New York: Five-time champion Roger Federer and 2012 winner Andy Murray head the US Open line-up on Thursday while 2001 champion Lleyton Hewitt could play his final match at the tournament.
World number two Federer, who reigned supreme in New York from 2004-2008 and was runner-up in 2009, faces Belgium`s Steve Darcis, the man who dumped Rafael Nadal out of Wimbledon in the first round in 2013.
Federer, 34, bidding to become the oldest men`s champion since Ken Rosewall in 1970, and clinch an 18th major, breezed through his opener against Leonardo Mayer in just 77 minutes on Monday.
It will be the Swiss star`s first meeting with world number 66 Darcis, who revels in his nickname of "Shark."
The 31-year-old Darcis is bidding to make the third round of a major for the first time. Federer has never lost before the fourth round in New York.
Murray, the third seed, got past controversial Australian Nick Kyrgios in four sets in his first round.
The 28-year-old Scotsman takes on French world number 35 Adrian Mannarino, a left-hander who has twice made the third round.
Murray won their only other previous meeting at Indian Wells this year in straight sets.
Hewitt, who made his New York bow in 1999, faces fellow Australian and Davis Cup teammate Bernard Tomic, the 24th seed.
It will be Hewitt`s 60th and last career match at the tournament if he loses, as he has already announced he will retire after next year`s Australian Open.
"Just awkward. That`s the only thing to summarise that," said Hewitt on facing his compatriot, who will line up with him at the Davis Cup semi-final against Britain later this month.
"I get along great with Bernie. Helped him out a lot. Hit with him this week. Yeah, just awkward."
"I don`t like playing any of the Aussies. I had to play (Thanasi) Kokkinakis last year in Brisbane. I played Grothy (Sam Groth) in Brisbane this year.
"I had to play J.P. Smith only a couple of weeks ago. For me, in the position that I`m in now, trying to help these guys especially with Davis Cup and the rest of it, yeah, it`s tough."
Also in action Thursday is Swiss fifth seed and French Open champion Stan Wawrinka, who faces South Korean teenager Hyeon Chung.
In the women`s draw, second seed Simona Halep faces Ukraine qualifier Kateryna Bondarenko, who is playing the US Open for the first time since 2012 after taking time out to have her first baby.
Former finalists and world number one players Caroline Wozniacki and Victoria Azarenka also eye third round places.
Fourth-seeded Wozniacki plays Petra Cetkovska of the Czech Republic while Azarenka opens proceedings on Arthur Ashe Stadium against Yanina Wickmayer of Belgium.