NEW YORK -- Some players, including top-ranked Simona Halep, freely acknowledge that they don't deal well with the hustle and bustle of the US Open and all it entails.

Others, such as 44th-ranked Kaia Kanepi, take to the Big Apple and its Grand Slam tournament.

Put those two types at opposite ends of a court at Flushing Meadows, and watch what can happen: Halep made a quick-as-can-be exit Monday, overwhelmed by the power-based game of Kanepi 6-2, 6-4 to become the first No. 1-seeded woman to lose her opening match at the US Open in the half-century of the professional era.

On a Day 1 that featured the major tournament debut of 25-second serve clocks, Halep blamed opening-round jitters, a recurring theme throughout her career. The reigning French Open champion has lost her first match at 12 of 34 career major appearances, a stunningly high rate for such an accomplished player.

"It's always about the nerves," said Halep, who was beaten in the first round in New York by five-time major champion Maria Sharapova in 2017. "Even when you are there in the top, you feel the same nerves. You are human."

She also offered an explanation tied to this particular site.

"Maybe the noise in the crowd. The city is busy. So everything together," said Halep, who was coming off consecutive runs to the final in hard-court tune-up tournaments at Cincinnati and Montreal. "I'm a quiet person, so maybe I like the smaller places."

Her departure means she can't stand in the way of Serena Williams, who could have faced Halep in the fourth round. Williams, the 23-time major champion who missed last year's US Open because she gave birth on Sept. 1, returned with a flourish, following singer Kelly Clarkson's opening-night performance in Arthur Ashe Stadium with a 6-4, 6-0 victory over Magda Linette under the lights.

"The first set was tight. It was my first back here in New York, so that wasn't the easiest," Williams told the crowd. "Once I got settled, I started doing what I'm trying to do in practice."

Serena hit six aces, won all eight of her service games and compiled a 23-9 edge in winners. Seeded 17th, Serena moved into a second-round meeting with 101st-ranked Carina Witthoeft of Germany. Win that, and Serena could face a familiar foe in the third round: her older sister, Venus, a two-time US Open champion who is seeded No. 16 and edged 2004 champ Svetlana Kuznetsova 6-3, 5-7, 6-3 Monday.

It would be the earliest matchup for the Williams siblings at a Grand Slam tournament in two decades. Their first all-in-the-family showdown came in the second round of the 1998 Australian Open.

"Hopefully,'' Venus said, "we'll both be there.''

Others making the second round included defending champion and No. 3 seed Sloane Stephens, two-time finalist Victoria Azarenka and two-time major champ Garbine Muguruza.

Halep's loss was the first match at the rebuilt Louis Armstrong Stadium, which has about 14,000 seats and a retractable roof, and what a way to get things started. That cover was not needed to protect from rain on Day 1 at the year's final major tournament, though some protection from the bright sun and its 90-degree (33-degree Celsius) heat might have been in order.

"The courts suit my game, and I love being in New York. I like the city," said Kanepi, who is from Estonia and is sharing a coach this week with another player, Andrea Petkovic. "I like the weather: humid and hot."

But several players had trouble in the heat, struggling with cramping or simply breathing.

Since professionals first were allowed to enter Grand Slam tournaments in 1968, only five times before Monday did women seeded No. 1 lose their opening match at a major -- and never at the US Open. It happened twice to Martina Hingis and once to Steffi Graf at Wimbledon, once to Angelique Kerber at the French Open and once to Virginia Ruzici at the Australian Open.

Halep got off to a slow start at Roland Garros this year, too, dropping her opening set, also by a 6-2 score, but she ended up pulling off a victory there and adding six more to lift the trophy.

There would be no such turnaround for her against Kanepi, a big hitter who dictated the points to claim her second career win against a top-ranked player -- but first top-20 victory since 2015. Kanepi has shown the occasional ability to grab significant results, including a run to the quarterfinals at Flushing Meadows a year ago.

On this day, Kanepi took charge of baseline exchanges, compiling a 26-9 edge in winners, 14 on her favored forehand side alone. Wearing two strips of athletic tape on her left shoulder, the right-handed Kanepi also had far more unforced errors, 28-9, but that high-risk, high-reward style ultimately paid off.

"I thought, 'I just have to be aggressive and try to stay calm,'" Kanepi said.

Early in the second set, on the way to falling behind by two breaks at 3-0, Halep slammed her racket twice, drawing a warning for a code violation from the chair umpire.

Eventually, Halep got going a bit, taking advantage of Kanepi's mistakes to break back twice and get to 4-all in that set, getting a lot of support from fans who repeatedly chanted her first name.

"I was thinking about that: Why [did] they cheer so much for her? Because normally, they cheer for the underdog," Kanepi said with a smile. "It was a bit annoying for some time, but I got over it."

Sure did. She ended a 14-stroke exchange with a crosscourt forehand volley winner to break right back for a 5-4 lead, then served out the victory.

The Associated Press contributed to this report.