Serena Williams will face Danka Kovinic in the first round as the American great begins her final US Open campaign.
It will be a final grand slam for 40-year-old Williams, who has won six singles titles in New York and been a runner-up on four occasions.
Her first singles crown in a major came as a 17-year-old at Flushing Meadows, when she beat Martina Hingis in the 1999 final.
Now the end of a glorious career is beckoning for the 23-time singles major winner, who has also landed 16 doubles grand slam titles.
Kovinic is the world number 80 from Montenegro, with the 27-year-old having only won two matches at the US Open in four previous main-draw appearances.
The winner of that match will likely face Estonian second seed Anett Kontaveit in round two. Kontaveit's first-round opponent will be Romanian Jaqueline Adina Cristian.
Defending champion Emma Raducanu, who was a shock winner last year, faces a tricky first-round assignment against France's Alize Cornet.
Cornet is the tour veteran who beat Iga Swiatek at Wimbledon, ending the Pole's 37-match winning streak, and this will be her 64th consecutive grand slam appearance, a record for WTA Tour players.
World number one Swiatek starts against Italian Jasmine Paolini and could face 2017 US Open champion Sloane Stephens in round two.
Former champion Naomi Osaka, unseeded this year, was paired with Danielle Collins, the 19th seed who was an Australian Open runner-up at the start of the year.
The tournament gets under way on Monday.
Men's defending champion Daniil Medvedev faces American Stefan Kozlov in his opener, while Rafael Nadal, who has not lost a grand slam match all year, faces Australian wild card Rinky Hijikata.
Nadal won the Australian Open and French Open titles before pulling out of Wimbledon ahead of his semi-final against Australian Nick Kyrgios due to an abdominal tear.
That handed Kyrgios a bye through to face Novak Djokovic, who got the better of the Australian, but the Serbian must miss the US Open because his refusal to be vaccinated against the COVID-19 virus meant he would not be allowed to enter the United States.
Djokovic's absence was confirmed shortly before the draw was revealed.
Fast-rising Spanish teenager Carlos Alcaraz begins against Argentina's Sebastian Baez, while fourth seed Stefanos Tsitsipas will face a yet-to-be-determined qualifier.
Raducanu stunned by qualifier Carle in Madrid
Maria Lourdes Carle made a splash at the Madrid Open on Wednesday, as the qualifier sent Emma Raducanu packing.
World number 82 Carle stepped into the void to fill in for Karolina Pliskova, who withdrew prior to the end of the qualifying rounds, to face 2021 US Open champion Raducanu.
It is just the second time Carle has reached the main draw of a WTA 1000 event, and she ensured it would be a memorable campaign after a 6-2 6-2 victory over Raducanu, who is now ranked at world number 221, though has enjoyed something of a return to form this season.
Raducanu reached the quarter-finals of the Stuttgart Grand Prix last week, going down to world number one Iga Swiatek, but has recently enjoyed victories over the likes of Angelique Kerber and Caroline Garcia.
Data Debrief
Carle is the first player from Argentina to defeat a former women's singles grand slam Champion since Nadia Podoroska overcame Serena Williams in Rome in 2021.
The 24-year-old is making just her sixth WTA main draw appearance, with her first WTA 1000 appearance having come in Miami in March.
'I will play Roland Garros if I feel competitive' – Nadal uncertain on French Open participation
Rafael Nadal is unsure as to whether he will be fit enough to feature at the French Open.
Nadal is embarking on a swansong season, having indicated he will retire after the 2024 campaign.
The 37-year-old is set to make his farewell appearance at the Madrid Open this week, with his campaign starting against American teenager Darwin Blanch on Thursday.
Nadal, now ranked 512 in the world, has played just five Tour-level matches this year, as he makes his comeback from yet another injury lay-off.
And the 14-time Roland Garros champion acknowledged on Wednesday that he would be unlikely to play at the French Open should it be taking place this week.
"If I was in Paris today, I wouldn't go out to play," he said.
"I don't think I'll be able to play at 100 per cent, but it's important to be able to play for the last time in Madrid.
"It means a lot to me to play on this court where I've had some great moments."
Thankfully for Nadal, the French Open does not take place until late May, giving him time to get fit.
"If I arrive in Paris the way I feel today, I will not play," he said.
"I will play Roland Garros if I feel competitive. If I can play, I play. If I can't play, I can't. It won't be the end of the world or the end of my career. I still have goals after Roland Garros, like the Olympics.
"Few weeks [ago], I didn't know if I would be able to play again on the professional tour. It's not perfect but at least I am playing and I can enjoy again, especially in the tournaments that are so emotional for me.
"I'm able to enjoy the fun that I can say, probably, goodbye on court. Without trying to confuse anyone, I don't know what's going to happen in the next three weeks.
"I'm going to do the things I have to do to be able to play in Paris. And if I can, I can and if I can't, I can't. I'm going to Paris if I feel like I'm good enough. I'm going to Paris if I feel capable enough to compete."
Nadal played three times in Brisbane in January, losing to qualifier Jordan Thompson and subsequently missing the Australian Open.
He featured twice in Barcelona earlier in April, losing to Alex De Minaur in the round of 32.
Nadal has won five titles in Madrid, though, and the tournament holds a special place for him, as he underlined his determination to compete.
He added: "Some moments I find myself enjoying being on court, playing against the best players again and I feel myself, more or less competitive, and other moments I feel limitations and it’s difficult.
"The goal is to be on court, enjoy it as long as possible. I mean, that's the thing, enjoy the fact that I will be able to compete one more time on the professional tour and here at home in Madrid, a place that gives me everything in terms of support.
"I am here giving myself a chance. If at some moment my situation improves, if I am able to find better feelings in my body, I need to be ready."
Osaka storms to victory in Madrid opener to end long wait for win on clay
Naomi Osaka comprehensively dispatched Greet Minnen on Tuesday to make a winning start to her Madrid Open campaign and earn a first win on clay for two years.
Japanese star Osaka triumphed 6-4 6-1 in only 79 minutes, swiftly booking a second-round clash against Liudmila Samsonova.
Osaka reached the last 32 at the WTA 1000 events on the hard courts of Indian Wells and Miami but had lost to Martina Trevisan at the first hurdle in the Open de Rouen on clay at WTA 250 level last week.
This was therefore a welcome return to form against Belgian qualifier Minnen and represented her first triumph on the surface since beating Anastasia Potapova at this tournament in 2022.
After an even start to the contest, the first set was level at 4-4. But Osaka then assumed full control, winning eight of nine games to race to victory.
Data Debrief: Osaka dominates on serve
Osaka was not broken at all in the match and allowed Minnen only one break-point opportunity across the whole contest.
She fired down eight aces to only three double faults, and won 13 of her 16 first-serve points in the second set.
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