Former champion Marin Cilic's has been bundled out of the US Open after going down in the third round to Argentine counter-puncher Diego Schwartzman.
Cilic, who skipped warm-up tournaments due to injury, was beaten 4-6 7-5 7-5 6-4 by the 29th seeded Schwartzman.
The Croatian fifth seed hit 80 unforced errors in an untidy display, three years after he lifted the trophy at Flushing Meadows.
Meanwhile women's third seed Garbine Muguruza easily progressed into the fourth round with a 6-1 6-1 demolition of Slovakian Magdalena Rybarikova to set up an exciting clash with Petra Kvitova.
The Spanish Wimbledon champion barely broke sweat on Louis Armstrong Stadium against the 31st seed.
Muguruza, one of the pre-tournament favourites, dropped serve once, the only glitch in a neat display.