Muguruza then enjoyed the greatest achievements of her career in the following six years, winning the 2016 French Open and the 2017 Wimbledon Championships (defeating Serena and Venus Williams in the finals, respectively), reaching the world No.

[8] At the US Open, she qualified into the main draw of a Grand Slam tournament for the first time after a number of players withdrew; she lost in three sets to tenth seed Sara Errani in the first round.

At the Australian Open, Muguruza made it into the main draw, after several players withdrew that did not pass into the qualifying match, she lost to Serena Williams in straight sets in the second round.

Muguruza recovered from her first-round defeat at the Monterrey Open by reaching the semifinals of the Marrakech Grand Prix where she lost to the eventual champion, María Teresa Torró Flor in straight sets.

[15] Muguruza also reached the semifinals of the doubles event with Suárez Navarro, where the pair lost in three sets to the top seeds and eventual champions, Peng Shuai and Hsieh Su-wei.

[17] Seeded 16th in the doubles event with Suárez Navarro, Muguruza and her partner defeated Ajla Tomljanović and Christina McHale, and Monica Niculescu and Klára Koukalová to reach the third round where they lost in straight sets to Andrea Petkovic and Magdaléna Rybáriková.

[26] At the Connecticut Open, Muguruza upset seventh seed Sara Errani[27] before defeating qualifier Peng Shuai[28] to reach the quarterfinals where she lost in three sets to unseeded Camila Giorgi.

She and Suarez Navarro also reached the third round of the doubles event, defeating Alizé Cornet and Kirsten Flipkens and Marina Erakovic and Arantxa Parra Santonja en route before losing to the unseeded Williams sisters.

[40] At the following week's China Open, Muguruza suffered a three-set first-round loss to Ekaterina Makarova[41] but reached the quarterfinals of the doubles event with Suárez Navarro.

[48] At the Australian Open, she progressed to the fourth round for the second consecutive year with wins over Marina Erakovic, Daniela Hantuchová and Timea Bacsinszky before falling to the eventual champion, Serena Williams, in three sets.

Despite failing to win back-to-back matches since February, Muguruza reached her second consecutive French Open quarterfinal, defeating Angelique Kerber[49] and Flavia Pennetta[50] en route, before losing to the eventual runner-up, Lucie Šafářová.

Muguruza kicked off the Asian swing at the Pan Pacific Open where she advanced to the last eight after defeating Barbora Strýcová before losing to eventual finalist Belinda Bencic, in straight sets.

She then went on to defeat the likes of Anna Karolína Schmiedlová and Kerber to reach the final where she faced Venus Williams but was forced to retire in the second set with an ankle injury.

She then went on to reach her first WTA semifinals of the season in Rome, after defeating top ten opponent Timea Bacsinszky in quarterfinals, but lost to Madison Keys in straight sets.

After that, she easily reached her second major final without losing a set in the next five matches, including wins over former champion Svetlana Kuznetsova in the fourth round, surprise quarterfinalist Shelby Rogers, and former runner-up Sam Stosur in the semifinals.

At the Australian Open, Muguruza beat Marina Erakovic, Samantha Crawford, Anastasija Sevastova and Sorana Cîrstea en route to her first quarterfinal at the tournament.

Muguruza suffered early losses at the start of the clay-court season, losing in her opening matches in Stuttgart and Madrid to Anett Kontaveit and Timea Bacsinszky, respectively.

This prompted a huge reaction in the Spanish sporting press, with some making the comment that "The Suzanne Lenglen Court looked more like the Stade de France, and it was as if there was a football game going on and not a tennis match".

Prior to Wimbledon, Muguruza began her grass-court season at the Birmingham Classic where she beat Elizaveta Kulichkova, Alison Riske and CoCo Vandeweghe before losing in the semi-finals to eventual runner-up Ashleigh Barty.

[70] In her first event back with Martínez, Garbiñe reached the Qatar Open final, recording wins over Duan Yingying, Sorana Cîrstea, and Caroline Garcia en route.

[80] At French Open, she defeated Svetlana Kuznetsova, Fiona Ferro, Sam Stosur, Lesia Tsurenko, and Maria Sharapova to reach the semifinals, where she lost to eventual champion Simona Halep.

47, Alison Van Uytvanck, and thus suffered the earliest defeat of a defending women's champion at the All England Club since Steffi Graf lost in the first round in 1994[83] Muguruza finished her 2018 season with her ranking at a low of 18.

Following the suspension of the WTA Tour due to the COVID-19 pandemic, she participated in the US Open, where she defeated Nao Hibino, before losing in the second round to a returning Tsvetana Pironkova, despite leading by 5–2 in the first set.

She next participated at Rome, where she defeated Sloane Stephens, Coco Gauff, Johanna Konta, and Victoria Azarenka, before losing in three sets to the eventual champion, Simona Halep.

In her next tournament at the Yarra Valley Classic, Muguruza dropped a total of ten games in matches against Alison Van Uytvanck, Anastasia Pavlyuchenkova, Sofia Kenin, and Markéta Vondroušová to make her first tour final since the 2020 Australian Open.

She then played the Qatar Open where she defeated in-form Russian Veronika Kudermetova, upset third seed and defending champion Aryna Sabalenka and avenged her Abu Dhabi loss to Maria Sakkari to make the semifinals.

Seeded ninth, she reached the quarterfinals with straight set wins over Irina-Camelia Begu, Amanda Anisimova and recent French Open champion Iga Świątek.

[103] She took on her last tournament of the year at the Kremlin Cup in Moscow and won over Tereza Martincová in three sets in the second round before she was a dealt a straight-set breadstick defeat by eventual champion Anett Kontaveit in the quarterfinals.

[127] Muguruza announced plans to help the organisation grow its impact in the areas of early grade literacy and equal access to secondary education for girls.

[130] 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)