Top seed Amelie Mauresmo bids to move a step closer to her third grand slam title of the year when she plays Russian 12th seed Dinara Safina on Wednesday for a place in the semi-finals.
After only one match was completed on Tuesday because of rain, the women's semi-final line-up will be decided with two men's quarter-finals and four fourth-round matches to be resolved.
Mauresmo takes on Safina after beating twice former champion Serena Williams in the fourth round.
The world number one is hoping to win her third grand slam title this year following victories over Justine Henin-Hardenne in the Australian Open and Wimbledon finals.
Second seed Henin-Hardenne takes on former champion Lindsay Davenport for the right to meet 19th seed Jelena Jankovic, and third seed Maria Sharapova faces French 27th seed Tatiana Golovin.
In the men's event, former champions Andy Roddick and Lleyton Hewitt square off for a place in the semi-finals.
Their match is a repeat of the 2001 quarter-final which Hewitt won in five sets. The Australian has won six of their eight career matches, although Roddick won the most recent, in Cincinnati last year.
Second seed Rafael Nadal, in the quarter-finals for the first time, takes on Russian Mikhail Youzhny in the day's other quarter-final.
In fourth-round action, top seed Roger Federer will continue his bid to win a third consecutive US Open title when he takes on little-known Frenchman Marc Giquel.
Giquel upset 21st seed Gaston Gaudio in the third round but world number one Federer has not dropped a set in his first three matches and is well on course to follow John McEnroe and Ivan Lendl in winning three straight years at Flushing Meadows.
Fifth seed James Blake bids to reach the quarter-finals for the second year in succession when he faces Tomas Berdych of the Czech Republic.
Scottish teenager Andy Murray has an uphill battle if he is to reach the last eight of a grand-slam event for the first time when he resumes his match with Russian Nikolay Davydenko, trailing the seventh seed two sets to one.
Another Russian, former champion Marat Safin, resumes 2-1 up with a break against German 14th seed Tommy Haas.