Serena Williams marked her return to the US Open with victory but Simona Halep became the first women's top seed to lose in the opening round in the Open era.
The world No.1 was scheduled first on the new Louis Armstrong Stadium against Kaia Kanepi and lasted just an hour and 15 minutes before succumbing to a 6-2 6-4 defeat.
At the end other end of the day, Williams opened the night session on Arthur Ashe and proved too strong for Poland's Magda Linette, winning 6-4 6-0.
It was her first match at Flushing Meadows since a semi-final loss to Karolina Pliskova in 2016, having given birth to daughter Olympia during the tournament 12 months ago.
Williams has had a difficult build-up to the tournament, suffering her most one-sided loss ever when she won just a single game against Johanna Konta in San Jose - she subsequently revealed she had learned just before the match that the man who killed her half-sister had been released from prison.
Williams then lost to Petra Kvitova in the second round in Cincinnati but pulled away here after a tight opening to the match and needed just an hour and nine minutes to clinch victory.
The 36-year-old, who is looking to equal Margaret Court's all-time record of 24 slam singles titles, said: "It's such a good feeling to be back out here.
"The first set was tight. Once I got settled, I started doing what I'm trying to do in practice, so it helped a lot. I think I'm getting there. I've been feeling really good in practice."
Williams could face a third-round meeting with sister Venus, who won a tough battle against fellow former US Open champion Svetlana Kuznetsova 6-3 5-7 6-3, but Halep is no longer in her section following her shock loss.
It was a tough draw against big-hitting Kanepi, who is a six-time grand slam quarter-finalist, and Halep simply could not find her rhythm as she slipped to a second successive first-round loss having been beaten by Maria Sharapova 12 months ago.
"I never play my best tennis here, even if I did quarter-finals, semi-finals," said Halep.
"Today just was not my day, the balance was not there. I couldn't feel myself strong on the court to win this match. It is tough. But it's OK."
Defending champion Sloane Stephens eased into the second round with a 6-1 7-5 victory over Russian Evgeniya Rodina.
The third seed said: "The first round of a grand slam is super tough, especially as defending champion. I'm super excited to get the tournament going."
Two-time Australian Open champion Victoria Azarenka is back in New York for the first time in three years as a wild card after the birth of son Leo and then the custody battle that limited her travel, and she battled to a 6-3 7-5 victory over Viktoria Kuzmova.
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