Croatia's Marin Cilic, the 2014 champion, faces Romanian Marius Copil, while fourth seed Alexander Zverev takes on Canada's Peter Polansky.
Women's second seed Caroline Wozniacki plays Australia's former champion Samantha Stosur in the day's first match on Arthur Ashe, and will hope to avoid the same fate as world number one Simona Halep who made a shock exit at the hands of unseeded Estonian Kaia Kanepi.
Fourth seed Angelique Kerber, who won Wimbledon this year, opens her campaign against Russia's Margarita Gasparyan, while France's Caroline Garcia takes on hard-hitting Briton Johanna Konta.
Australian bad boy Nick Kyrgios will play the first match of the evening session at the Louis Armstrong Stadium against Moldovian Radu Albot while Maria Sharapova, who is seeded 22nd this year, faces Switzerland's Patty Schnyder.
Madison Keys and Frances Tiafoe are the two home hopes in action on the main showcourts, with 14th seed Keys playing France's Pauline Parmentier in the last match on Arthur Ashe. The unseeded Tiafoe faces Frenchman Adrian Mannarino on Grandstand.
(Reporting by Simon Jennings; Editing by Ian Ransom)
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