Former champions Carlos Alcaraz and Naomi Osaka were knocked out of the US Open on Thursday as the final Grand Slam of the year lost two of its biggest crowd-pullers.

Alcaraz, the world number three and 2022 champion in New York, was stunned by Dutch world number 74 Botic van de Zandschulp 6-1, 7-5, 6-4.

Osaka, who counts the 2018 and 2020 US Opens amongst her four career majors, slipped to a 6-3, 7-6 (7/5) loss at the hands of 52nd-ranked Czech Karolina Muchova.

Alcaraz had made at least the quarter-finals in his three previous appearances in New York. Thursday's defeat was his earliest at a Grand Slam since a second round exit at Wimbledon in 2021.

Defeat ended his dream of becoming only the third man in the modern era to win the French Open, Wimbledon and the US Open in the same season.

"The tennis schedule is so tight. I've been playing a lot of matches lately with Roland Garros, with Wimbledon, Olympic Games," said Alcaraz who lost a draining Olympics final to Novak Djokovic in Paris just over three weeks ago.

"I took a little break after the Olympic Games. Probably it wasn't enough. Probably I came here with not as much energy as I thought that I was going to come. But I don't want to put that as excuse."

- 'Incredible evening' -

Van de Zandschulp said he was lost for words after only his second career win over a top five player.

"It was an incredible evening out here in my first time in the night session on Arthur Ashe," he said.

"I tried to stay calm. You have to keep your head against these guys otherwise they will take advantage."

He broke twice in the opening set to stake his claims in front of a shell-shocked crowd.

He was breaks to the good in sets two and three, leaving Alcaraz to counter-punch before surrendering his hard-earned foothold.

His fate was sealed when he committed his 27th and final unforced error of the night as van de Zandschulp pulled off one of the biggest upsets in recent Grand Slam history.

The Dutchman, who had lost his two previous matches with Alcaraz, will next face 25th-seeded Jack Draper.

For Osaka, her comeback from maternity leave remains stalled.

She missed last year's tournament after giving birth to daughter Shai but made up for that absence in the first round when she brushed aside Jelena Ostapenko for a first top 10 win in four yeats.

However, on Thursday the 26-year-old went down to a straight sets loss to 2023 semi-finalist Muchova, leaving her without a third round appearance at the majors since the 2022 Australian Open.

Osaka blew three set points in the second set before a wild forehand handed her Czech rival victory.

"It's been a little difficult because obviously I can only gauge how I'm doing by results. I feel faster. I feel better, but I lost in the second round. So it's a little rough," said Osaka.

Muchova will meet Russia's Anastasia Potapova for a last 16 spot.

"Honestly this year the biggest win for me is that I could play again," said Muchova who picked up a wrist injury at last year's US Open which sidelined her for nine months.

Alcaraz's defeat removed a major title barrier from the path of top seed Jannik Sinner, who had been scheduled to meet the Spaniard in the semi-finals.

World number one Sinner won his 50th match of the year when he defeated America's 49th-ranked Alex Michelsen 6-4, 6-0, 6-2 to make the last 32 for a fourth successive year.

The 23-year-old Italian unleashed 28 winners and broke serve eight times. He will face Australia's Christopher O'Connell for a place in the last 16.

Women's world number one Iga Swiatek charged into the third round, routing 217th-ranked Ena Shibahara of Japan 6-0, 6-1 to record her 55th match win of 2024.

Poland's Swiatek, the 2022 US Open winner who is seeking to add a second title in New York to her four French Open triumphs, overwhelmed the 26-year-old qualifier, who was in the main draw of a Grand Slam for the first time, in just 65 minutes.

She goes on to face 25th seed Anastasia Pavlyuchenkova who was a quarter-finalist in New York 13 years ago.

- Rybakina withdraws -

Swiatek then saw likely semi-final opponent Elena Rybakina withdraw from the tournament ahead of her second round clash with 143rd-ranked French qualifier Jessika Ponchet.

Rybakina issued a statement saying she was forced to withdraw "because of my injuries".

Karolina Pliskova, the 2016 runner-up, suffered a left ankle injury and was forced to retire from her match with fifth-seed Jasmine Paolini after just three points.

Fourth seed and 2021 champion Daniil Medvedev defeated Hungary's Fabian Marozsan in straight sets