Following two more major titles, in 2021, Osaka suffered from depression and other issues, which led to a publicly-scrutinized retirement from the French Open and withdrawal from Wimbledon.

She was named one of the 2020 Sports Illustrated Sportspersons of the Year for her activism, particularly during her US Open championship run, and was included on Time's annual list of the 100 most influential people in the world in 2019, 2020, and 2021.

[12] She entered her first two qualifying draws on the WTA Tour that same month at the Challenge Bell in Quebec and the Pan Pacific Open in Tokyo.

[11] Following these runner-up results, Osaka was ranked high enough to enter qualifying at the last two Grand Slam singles events of the year, Wimbledon and the US Open.

In October during the WTA Finals, she won the Rising Stars Invitational four-player exhibition tournament, defeating heavy favorite and world No.

At the Australian Open, she reached the fourth round after defeating two top-20 players in Elena Vesnina and hometown favorite Ashleigh Barty, ultimately losing to world No.

[44][45] She then closed out the tournament with a win in the final over fellow up-and-coming player Daria Kasatkina, making her the youngest champion at the event in ten years.

[16] Osaka played the following week as well at the Miami Open and extended her win streak by one additional match in her first meeting against her childhood idol, Serena Williams, who was competing in just her second tournament back from maternity leave.

2 Karolína Plíšková in a semifinal at the Brisbane International and Coco Gauff in the third round of the Australian Open, squandering a chance to serve for the match in the former.

She had initially withdrawn from the Cincinnati Open before the semifinal to raise awareness for the police shooting of Jacob Blake, only staying in the tournament after they chose to support her cause by postponing the event for a day.

[92] At the US Open, Osaka walked onto the court for her seven matches wearing a different black mask, each of which with the name of an African American who had been killed in recent years often without significant repercussions.

She went on to defeat Hsieh Su-wei in the quarterfinals, Serena Williams in the semifinals, and 22nd seed Jennifer Brady[94] in the final to claim her second Australian Open title.

[101] Many fellow athletes and sponsors have voiced support for Osaka, with some noting a rarely discussed issue of mental health, although the overall reaction from the wider tennis community was mixed.

[111] In March, Osaka entered the Indian Wells Open where she beat Sloane Stephens in the first round, but lost to Veronika Kudermetova in straight sets in the second.

In Miami, Osaka took out Italian player Elisabetta Cocciaretto and Ukrainian Elina Svitolina in straight sets before falling to Frenchwoman Carolina Garcia in their third face-off of the year.

[132] She reached the fourth round in Rome, defeating notably seeded Daria Kasatkina and Marta Kostyuk in straight sets,[133] before falling to Zheng Qinwen.

She made a winning return and beat fourth-seeded Elise Mertens in the first round,[136] eventually making it to the quarterfinals where she was defeated by Bianca Andreescu.

[143] Osaka played her next tournament at the China Open, making it through to the fourth round where she retired due to a back injury at the start of the third set against Coco Gauff.

[145] Osaka started her 2025 season at the Auckland Open, where she reached the final but retired due to an abdominal injury after winning the first set against 5th-seeded Clara Tauson.

[7] Following her loss at the 2016 US Open where she could not convert a 5–1 lead in the third set, the Japan Tennis Association helped arrange for David Taylor to be her new coach.

[156] After the 2017 season, Osaka switched coaches to Sascha Bajin, who had previously served as a hitting partner to top players such as Serena Williams, Victoria Azarenka, and Caroline Wozniacki.

[182] In 2022, Osaka left IMG, in order to set up her own sports management agency, Evolve, alongside her agent, Stuart Duguid.

[180][183] She also endorses several other Japanese companies, including noodle maker Nissin Foods, cosmetics producer Shiseido, the broadcasting station Wowow, and airline All Nippon Airways (ANA).

[187][188] In January 2021, Osaka was named the brand ambassador for Tag Heuer watches, as well as for Louis Vuitton; she appeared in their Spring-Summer 2021 campaign.

[189] She is also endorsed by Beats Electronics, Bodyarmor SuperDrink, Mastercard, Panasonic, FTX, PlayStation, Levi's, Airbnb, Sweetgreen, Workday, and GoDaddy.

[191][192] In February 2022, the U.S. 11th Circuit Court of Appeals ruled in a lawsuit against Bitconnect that the Securities Act of 1933 extends to targeted solicitation using social media.

She outlined her personal reasons for supporting the Black Lives Matter movement and protesting against police brutality in an op-ed in Esquire magazine.

[201] She was also honored as one of the Time 100 most influential people in the world in 2020 for her activism, having also been named to the list in 2019 for representing professional tennis well as an excellent role model and a major champion.

[202][203] Osaka's activism has drawn attention from the scholarly community studying celebrity and advocacy, especially during the COVID-19 pandemic and following the police killing of George Floyd.

[231] [232] (Naomi withdraws in Second Round 2021 French Open) Chris Evert (1975/1985 – 260 w) Evonne Goolagong (1976 – 2 w) Martina Navratilova (1978/1987 – 331 w) Tracy Austin (1980 – 22 w) Steffi Graf (1987/1997 – 377 w) // Monica Seles (1991/1996 – 178 w) Arantxa Sánchez Vicario (1995 – 12 w) Martina Hingis (1997/2001 – 209 w) Lindsay Davenport (1998/2006 – 98 w) Jennifer Capriati (2001/2002 – 17 w) Venus Williams (2002 – 11 w) Serena Williams (2002/2017 – 319 w) Kim Clijsters (2003/2011 – 20 w) Justine Henin (2003/2008 – 117 w) Amélie Mauresmo (2004/2006 – 39 w) Maria Sharapova (2005/2012 – 21 w) Ana Ivanovic (2008 – 12 w) Jelena Janković (2008/2009 – 18 w) Dinara Safina (2009 – 26 w) Caroline Wozniacki (2010/2018 – 71 w) Victoria Azarenka (2012/2013 – 51 w) Angelique Kerber (2016/2017 – 34 w) Karolína Plíšková (2017 – 8 w) Garbiñe Muguruza (2017 – 4 w) Simona Halep (2017/2019 – 64 w) Naomi Osaka (2019 – 25 w) Ashleigh Barty (2019/2022 – 121 w) Iga Świątek (2022/2024 – 125 w) Aryna Sabalenka (2023/2024 – 9 w)