Serena Williams has the US Open spotlight as she chases tennis history, but a host of Grand Slam winners and high-ranked rivals are also taking aim at the title.

The 37-year-old American will be the focus of attention when the Flushing Meadows fortnight begins Monday with her first-round night match against Russian Maria Sharapova the most anticipated of the women's openers.

"Of course I'm going to watch it," said top-seeded defending champion Naomi Osaka, who beat Williams in last year's US Open final. "I think everyone in New York is going to watch it.

"I'm not that surprised that that happened, because at every Grand Slam there's always some sort of drama. Like a first round. Like, Oh my God. So this match just happens to be that for this tournament."

Williams will try to capture her 24th Grand Slam singles title to match the all-time record set by Margaret Court.

Eighth-seeded Williams, who could meet second-seeded French Open champion Ashleigh Barty of Australia in the quarter-finals, has not won a Slam since the 2017 Australian Open when she was pregnant, losing the US Open final to Osaka last year amid controversy and the past two Wimbledon finals -- including last month to Romania's Simona Halep.

Barty, Osaka, Halep and Czech third seed Karolina Pliskova, seeking her first Slam title, are among the foes trying to deny Williams yet again in a quest she insists doesn't dominate her thoughts.

"I think it's definitely meaningful, but at this point in my career, I just try to think of different things and even bigger goals — so it's just like 24 is just a thing," Williams said earlier this month.

"There are so much more important things in my life. And obviously tennis is super important to me... but yeah there are always other things in life, I feel, that are really big on my plate too."

Williams has not played since retiring from the WTA Toronto final with back spasms, handing Canada's Bianca Andreescu the title.

"Definitely if she manages physically, then I think she can do really well here," Andreescu said.

"She'll do great, as she always does," added 2017 US Open winner Sloane Stephens.

Osaka 'very confident'

Osaka won last year's final after Williams was given a game penalty by umpire Carlos Ramos, who US Open officials have decided will not work on any match with Serena or Venus Williams at this year's US Open.

This time, Osaka has had a better run-up to the Open despite a first-round Wimbledon crash out.

"Last year I lost three matches in a row before I came here, so I just wanted to get one match. Then it just kept building on from that," she said.

"This year I went to two quarter-finals back to back and I feel very confident about how I am right now."

While it's Osaka's first time defending a Slam, she had her first taste of defending a title this year at Indian Wells.

"Going to Indian Wells and learning how defending champion pressure feels, I think it definitely helped me out going into this tournament," Osaka said. "Because I just feel more loose and comfortable here.

"I'm not sure if it's because the last couple of months have been kind of turbulent but definitely I feel really comfortable and I know that, despite everything, I play well here every year. So I'm not too worried about that."

And she's much better after pulling out in Cincinnati with a left knee injury.

"It's getting better. I've been playing more, longer every day," she said. "Luckily I'm a fast healer so I think it's looking good."

Halep's confidence high

Halep, who has crashed out of the US Open in the first round the past two years, enters with confidence after beating Williams at Wimbledon.

"It cannot be worse than the last two years, to lose in the first round," Halep said. "I'm really good. I'm feeling healthy. I'm feeling fresh.

"The pressure of doing something special, it's off. Now what comes, comes as a bonus. I'm still working, I'm still motivated to win titles. I've started to feel more and more that I'm capable to do that so my confidence is very high."

Barty says "nothing has really changed for me" since her title at Roland Garros.

"I just come here to play and do the best that I can," Barty said. "I'm focused on my first round on Monday and that's all I'm worried about for the moment."