Former Wimbledon champion Garbine Muguruza was knocked out of the US Open in the first round with a 2-6 6-1 6-3 defeat by Alison Riske.
American Riske, ranked 11 places below the Spaniard at 36th, sealed her first win at Flushing Meadows since 2013.
Two-time Wimbledon champion and sixth seed Petra Kvitova advanced by beating fellow Czech Denisa Allertova 6-2 6-4.
Former French Open champion Jelena Ostapenko and Swiss 13th seed Belinda Bencic are also through.
Latvia's Ostapenko overcame Serb Aleksandra Krunic 6-3 7-6 (7-9), while Bencic beat Luxembourg's Mandy Minella 6-3 6-2 on day two of the final Grand Slam of the year.