US Open champion Naomi Osaka was forced to dig deep in her first-round match, while former winner Sloane Stephens was a surprise casualty in New York.
Returning to the scene of her maiden grand slam title, world number one Osaka outlasted Anna Blinkova in three sets on Tuesday.
Wimbledon champion Simona Halep, former world number one Caroline Wozniacki and 15-year-old sensation Coco Gauff also reached round two, but Stephens headlined the exits.
OSAKA OVERCOMES NERVES IN NEW YORK OPENER
Top seed Osaka edged unseeded opponent Blinkova 6-4 6-7 (5-7) 6-2 in an unconvincing display at Flushing Meadows.
Osaka was not at her best, tallying 50 unforced errors, but the two-time grand slam champion still managed to book a second-round date with Magda Linette.
"I don't think I've ever been so nervous in my life," Osaka said during her on-court interview. "I don't think I ever really found my rhythm, but I just fought as hard as I can."
HALEP HANDLES LUCKY LOSER
Romanian star and fourth seed Halep prevailed 6-3 3-6 6-2 against lucky loser Nicole Gibbs.
Halep produced when it mattered most as she avoided becoming only the second player in the Open Era to follow up victory at Wimbledon with a first-round loss in New York.
Next up for Halep is qualifier Taylor Townsend, who rallied past Kateryna Kozlova 3-6 6-3 6-2.
Wozniacki, meanwhile, came from a set down to see off Wang Yafan 1-6 7-5 6-3 in an opening-round scare.
Runner-up in 2009 and 2014, 19th seed Wozniacki meets Danielle Collins in the second round after the 2019 Australian Open semi-finalist defeated Polona Hercog 6-3 4-6 6-4.
GAUFF'S STAR CONTINUES TO SHINE
The fairytale story of Wimbledon, Gauff fought past fellow teenager Anastasia Potapova 3-6 6-2 6-4.
Gauff rose to stardom at Wimbledon earlier this year, making the fourth round at the All England Club.
The American sensation emerged triumphant in her main-draw debut at her home major on Tuesday thanks to seven breaks of serve.
"It was crazy," said Gauff, who will play qualifier Timea Babos after 28th seed Carla Suarez Navarro retired at the end of the first set. "Obviously I was nervous going out on the court. It's such a big court. Then my home slam, so I wanted to do well. The crowd really helped me the whole match. Like, it was really a great atmosphere to play in and a great experience for me."
KALINSKAYA SLAYS SLOANE
There was a major upset in New York, where 2017 champion Stephens was sensationally eliminated 6-3 6-4 by qualifier Anna Kalinskaya.
Stephens hoped to enjoy another deep run at Flushing Meadows after reuniting with long-time coach Kamau Murray but Kalinskaya had other plans for the 11th seed.
Two-time grand slam winner and 24th seed Garbine Muguruza also fell at the first hurdle, knocked out 2-6 6-1 6-3 by Alison Riske.
Svetlana Kuznetsova – the 2004 champion – went down 7-5 6-2 to Kristie Ahn, while two-time finalist and former world number one Victoria Azarenka lost 3-6 6-3 6-4 to ninth seed Aryna Sabalenka.