Two-time US Open champion Naomi Osaka looks for a spot in the last 32 of a major for the first time in over two years.
Jannik Sinner and Carlos Alcaraz, who are seeded to meet in the semi-finals, are also in second round action.
AFP Sport looks at three matches to watch on day four of 2024's final Grand Slam, which will conclude on September 8.
Iga Swiatek vs Ena Shibahara
Top seed Swiatek, already with four French Opens to her name, seeks a second New York title to add to her 2022 triumph.
On Thursday, the Pole meets Japan's world number 217 Ena Shibahara who is making her Grand Slam singles main draw debut after battling through qualifying.
The California-born Shibahara, who arrived in New York with just one win on the main tour in 2024, defeated Australia's Daria Saville in the first round in a match which lasted three hours and 16 minutes, the longest women's clash so far.
"It was an emotional rollercoaster," she said.
Shibahara has already defeated Swiatek twice in her career, but those wins came in doubles at the 2016 US Open junior event and in 2021 in the Miami semi-finals.
Naomi Osaka vs Karolina Muchova
Naomi Osaka, the 2018 and 2020 champion at Flushing Meadows, swept past former French Open winner Jelena Ostapenko in the first round.
Four-time major winner Osaka, who missed the 2023 event after giving birth to daughter Shai, saved the only two break points she faced against the Latvian, served up nine aces and did not double fault.
The 26-year-old also made headlines for her colourful walk-on attire which featured a bright green bow and a tutu.
"When I was putting on my outfit today, I was, like, 'Ah, I hope this isn't too much'," Osaka said.
"Because I had the tutu and then I had the bow jacket and it was green, I feel like everyone was staring at me funny."
On Thursday, Osaka meets 2023 French Open runner-up Karolina Muchova who only returned to the tour in June this year after suffering a wrist injury during her run to the US Open semi-finals last year.
Carlos Alcaraz vs Botic van de Zandschulp
Alcaraz, the 2022 champion, is seeking to become only the third man in the modern era to win the French Open, Wimbledon and US Open in the same year.
He surprisingly needed four sets to see off Australian qualifier Li Tu in the first round where he became the second fastest man behind John McEnroe to reach 60 Grand Slam wins.
"It's an honour to be able to share these types of statistics with great legends of the sport," said Alcaraz.
The 21-year-old takes a 2-0 head-to-head record over 74th-ranked Van de Zandschulp into Thursday's second round match.
However, the Dutchman enjoyed his best Grand Slam run in New York in 2021 when he reached the quarter-finals where he lost in four sets to eventual champion Daniil Medvedev.
