It's the first time since 2004 that Nadal has missed out on all four grand slam quarter-finals
Rafael Nadal, the two-time US Open champions, has been knocked out in the fourth round by France's Lucas Pouille.
The 2010 and 2013 champion failed to drop a set in the opening three rounds, but lost to the number 24 seed in four sets. Pouille won a fifth-set tiebreak 8-6 after the two men shared the opening four sets.
Nadal's loss means he misses out on the quarter-finals for the second-year in a row. It is also the first time since 2004 that the 30-year-old has missed out a quarter-final appearance in any of the four Grand Slam tournaments.
Pouille's win sends him into the quarter-finals for the first time in New York. France will also be the best represented country in the quarter-finals as Pouille is joined by his opponent Gael Monfils and Jo-Wilfried Tsonga.
Top-seed Novak Djokovic is also into the quarter-finals. The Serbian defeated Great Britain's Kyle Edmund in straight sets. Djokovic has has a relatively comfortable path to the quarter-finals. After a four-set win in the first round, Djokovic was given a second-round walkover, before his third round opponent withdrew after six games in the third round.
In the women's draw, all four fourth round games on Sunday were won in straight sets. Germany's Angelique Kerber, the second seed, defeated two-time Wimbledon champion Petra Kvitova.
Eighth seed Madison Keys was the highest seed to fall on day seven. The American lost to Denmark's Caroline Wozniacki in just under an hour an 20 minutes.
Monday sees the Williams sisters, Serena and Venus, compete in their fourth round matches, with Andy Murray and Juan Martin del Potro looking to book their spots in the quarter-finals of the men's draw.