Rafael Nadal could face Roger Federer in the US Open quarter-finals while top-ranked Novak Djokovic is set for a potential semi-final clash against defending champion Andy Murray.
Seventh-seed Federer, a 17-time Grand Slam winner whose run of five US Open titles in a row was halted by Juan Martin Del Potro in the 2009 final, was on Thursday drawn into the same quarter as second seed Nadal, a 12-time major winner who completed a career Slam with his 2010 US Open title.
The top-ranked potential semi-final rivals for either Spaniard Nadal or Swiss star Federer would be Spanish fourth seed David Ferrer or French eighth seed Richard Gasquet.
In the other half of the draw, Serbia's Djokovic, the reigning Australian Open champion and the 2011 US Open winner, has a tough path to the September 9 men's final that would include a last-eight matchup against Argentina's Del Potro.
Djokovic might then have a semi-final against defending champion and third seed Murray of Britain just to reach the final, with Wimbledon winner Murray's highest-ranked opponent in his quarter being Czech fifth seed Tomas Berdych.
On the women's side, world number one and top seed Serena Williams could face eighth seed Angelique Kerber in the quarter-finals and either Polish third seed Agnieszka Radwanska or Chinese fifth seed Li Na in the semi-finals.
Second seed Victoria Azarenka of Belarus and Czech seventh seed Petra Kvitova were drawn into the same quarter of the field with possible opponents in the semi-finals including Italian fourth seed Sara Errani, a 2012 US Open semi-finalist, and Danish sixth seed Caroline Wozniacki.
Williams, who opens against Italy's former French Open winner Francesca Schiavone, could face US 15th seed Sloane Stephens in the fourth round and might meet sister Venus, a two-time US Open winner, in the quarter-finals.
Stephens defeated Serena Williams in the Australian Open quarter-finals back in January.
Two-time reigning Australian Open champion Azarenka, who opens against Germany's Dinah Pfizenmaier, has Czech seventh seed Petra Kvitova, the 2011 Wimbledon winner, and Australian 11th seed Samantha Stosur, the 2011 US Open champion, among her possible quarter-final foes.
Djokovic opens against Lithuania's Ricardas Berankis with a possible second-round match against German Benjamin Becker or Czech Lukas Rosol.
Del Potro opens against Spain's Guillermo Garcia-Lopez and could meet former US Open champion Lleyton Hewitt of Australia in the second round.
Murray's defending of his first Grand Slam title opens against Frenchman Michael Llodra with Romanian Victor Hanescu or Argentina's Leonardo Mayer his possible second-round opponents.
Spanish 15th seed Nicolas Almagro would be the Scotsman's highest-seeded potential rival in the fourth round.
Before Federer and Nadal could meet to decide a semi-final spot, they would have some work in the early rounds as well.
Nadal opens against US wildcard Ryan Harrison with Canada's Vasek Pospisil or a qualifier awaiting in round two and top US hope John Isner, the big-serving 13th seed, a possible fourth-round foe.
Federer opens against Slovenia's Grega Zemlja with a South American, Colombia's Santiago Giraldo or Argentina's Carlos Berlocq, awaiting in round two.
Japan's 11th-seeded Kei Nishikori is a possible Federer foe in the round of 16.