French Open winner Nadal has battled his way through the opening two rounds in New York.
He beat Dusan Lajovic in three sets in the first round but was pushed to four sets against Japan’s Taro Daniel in the second.
Roger Federer is also in action and plays Feliciano Lopez.
The Wimbledon champion has had an even harder time of it at Flushing Meadows, having been taken to five sets in both his matches.
Women’s No 1 seed Karolina Pliskova is first up on Arthur Ashe against China’s Shuai Zhang.
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Agnieszka Radwanska will play CoCo Vandeweghe after Pliskova before Nadal takes to the court.
Follow all the results as they drop in live through the day below.