Former US Open champion Naomi Osaka was pushed to three sets in the opening round, while top seed Karolina Pliskova also made it through on day one.
Osaka – who was crowned queen of Flushing Meadows in 2018 – was tested by fellow Japanese player Misaki Doi under the Arthur Ashe Stadium lights on Monday.
Pliskova saw off Anhelina Kalinina in the behind-closed-doors grand slam amid the coronavirus pandemic in New York.
However, American sensation Coco Gauff fell at the first hurdle.
OSAKA DISPATCHES DOI
Japanese star Osaka kicked off her bid to win a second US Open title with a 6-2 5-7 6-2 victory in the night session.
Osaka – the fourth seed – was challenged by Doi but the former world number one came through in two hours, two minutes.
In her first match since withdrawing from the Western & Southern Open final due to a hamstring injury, Osaka showed no ill effects – hitting 25 winners and 38 unforced errors while converting five of 11 break-point opportunities.
Next up for the 2019 Australian Open champion is Camila Giorgi, who outlasted Alison Van Uytvanck 2-6 6-1 7-5.
PLISKOVA OUTCLASSES KALININA
The 2016 US Open runner-up made it past the first round by beating Ukrainian Kalinina 6-4 6-0.
Pliskova was in command at 4-1 in the first set, but lost the next three games and had to fend off two break points to avoid going 5-4 down.
The world number three held and broke to love to take the first set before dominating the second in the Flushing Meadows bubble.
Pliskova will face Caroline Garcia in the second round after the 32nd seed beat Jasmine Paolini 6-3 6-2.
For the first time in her career, American teenager Gauff lost in the first round of a grand slam following a 6-3 5-7 6-4 defeat against 31st seed Anastasija Sevastova.
Gauff reached the fourth round at this year's Australian Open, but the 16-year-old crashed out at her home major.
KVITOVA, KERBER PROGRESS
Sixth seed and two-time Wimbledon champion Petra Kvitova eased past Irina-Camelia Begu 6-3 6-2.
Three-time grand slam winner Angelique Kerber – the 17th seed – made her first appearance since January and defeated Ajla Tomljanovic 6-4 6-4.