Olympic champion Zheng Qinwen fought back from a set down to beat world number 50 Amanda Anisimova 4-6 6-4 6-2 on Louis Armstrong Stadium.
Anisimova raced out to a 5-1 first-set lead but twice failed to serve it out, before breaking Zheng for the third time to clinch the opener.
But Zheng, a little over three weeks on from her Olympic triumph in Paris, recovered well and served superbly from then on.
The Chinese seventh seed said it was the “typical match” she would have lost in the past, adding that victory was “one step forward in my mental side”.
“Usually after huge success I will get a little bit too high, and until the reality slap me down again and I come back to the ground,” Zheng said.
“So this time when I get a success, I’m telling myself, I don’t want to let this happen. I’m really happy to get this match, because she’s really tough to face.”
Australian teenager Iva Jovic pulled off the biggest upset of the opening day in New York, with the 16-year-old beating world number 40 Magda Linette 6-4 6-3 for her first WTA match win.
Meanwhile, France’s Clara Burel claimed an impressive comeback victory against 2017 champion Sloane Stephens.
Stephens won the first nine games of the match in 33 minutes but Burel somehow clawed her way back from a break down in both the second and third set before wrapping up a 0-6 7-5 7-5 win.
Burel will face three-time runner up Victoria Azarenka of Belarus, who beat Ukraine’s Yulia Starodubtseva 3-6 6-1 6-1.
Daria Kasatkina, the 12th seed, beat Romania’s Jaqueline Cristian 6-2 6-4 to progress, while Ukrainian 27th seed Elina Svitolina came through in three sets against Maria Lourdes Carle of Argentina.
Wimbledon champion Barbora Krejcikova also progressed, beating Spanish qualifier Marina Bassols Ribera 7-6 (7-3) 6-2, while American 13th seed Emma Navarro beat Anna Blinkova 6-1 6-1 in just 59 minutes.
However, Maria Sakkari became the first top-10 player to fall, with the ninth seed forced to retire injured after losing the first set to Wang Yafan.
A visibly upset Sakkari received treatment from the trainer to her shoulder and neck midway through the first set, and was ultimately unable to continue into a second.
American 14th seed Madison Keys, runner-up at Flushing Meadows in 2017, moved past Katerina Siniakova of the Czech Republic 6-4 6-1.