In March, Muguruza lost to Ka. Plíšková in the third round of the Indian Wells Masters after a second round win over American wildcard Irina Falconi. Despite this, she rose to a career high singles ranking of world No. 19 after the event. A fortnight later, Muguruza reached the third round of the Miami Open after defeating qualifier Sesil Karatantcheva but lost to the eleventh seed Sara Errani after winning the first set.
Muguruza reached the second round of the three clay court events that she competed in leading into the French Open. She lost to second seed Simona Halep in Stuttgart, Kristina Mladenovic in Marrakech and the eventual finalist Svetlana Kuznetsova in Madrid. Muguruza and Suárez Navarro also reached the doubles final of the latter for the second consecutive year but the pair lost in three sets to Casey Dellacqua and Yaroslava Shvedova. Despite failing to win back-to-back matches since February, Muguruza reached her second consecutive French Open quarterfinal, defeating Angelique Kerber[5] and Flavia Pennetta[6] en route, before losing to the eventual runner-up, Lucie Šafářová.[7]
"For me if Muguruza doesn't win it this year, she's going to win this or another Grand Slam at some point. She's not waiting, she's going and getting it, and that's the only way you can lift a Grand Slam trophy."
Muguruza made a poor start to the grass court season, losing in the first round of the Birmingham Classic and the third round of the Eastbourne International after a first round bye. However, she and Suárez Navarro won their first grass court doubles title in Birmingham, defeating Andrea Hlaváčková and Lucie Hradecká in straight sets in the final. At the Wimbledon Championships, Muguruza defeated 10th seed Kerber in the third round,[10] 5th seed Caroline Wozniacki in the fourth round,[11] 15th seed Timea Bacsinszky in the quarterfinals and 13th seed Agnieszka Radwańska in the semi-finals to advance to her maiden Grand Slam final. She played against world No. 1 Serena Williams for the title, but lost in straight sets.[12] After the tournament, Muguruza entered the Top 10 for the first time, moving up to world No. 9 in the WTA Rankings.
During the US Open series, Muguruza did not enjoy much success, dropping her opening matches in Toronto and Cincinnati to qualifiers Lesia Tsurenko and Yaroslava Shvedova respectively. At the US Open, she recorded her first win at the tournament by defeating German Carina Witthöft in the first round. However, she fell short to Johanna Konta in the following round in three sets, the match was a total time of 3 hours and 23 minutes, the longest women's singles match in that tournament's history since the introduction of tiebreaker in 1970.
Muguruza kicked off the Asian swing at the Pan Pacific Open where she successfully advanced to the last eight after defeating Barbora Strýcová before losing to eventual finalist Belinda Bencic in straight sets. At the Wuhan Open, Muguruza successfully cruised into her second straight quarterfinal at the event after dispatching Sloane Stephens and Ana Ivanovic. She then went on to defeat the likes of Anna Karolina Schmiedlova and Kerber to reach the final where she faced Venus Williams but was forced to retire in the second set with an ankle injury. Muguruza was able to crack the Top 5 for the first time in her career after the tournament's conclusion.[13] At the China Open, Muguruza breezed by Irina Falconi before going the distance against Mirjana Lučić-Baroni to advance to the quarterfinals. With the win, Muguruza qualified for the WTA Finals for the first time. She will be the first Spaniard to compete at the year-end championships since Arantxa Sánchez Vicario in 2001. She then beat Bethanie Mattek-Sands and Radwańska to advance to her maiden Premier Mandatory final. With her semifinal win over Radwańska, Muguruza cracked the Top 4 rankings where she reached a career high of world No. 4. She went on to defeat Bacsinszky in straight sets to claim her first Premier Mandatory title and her biggest title of her career.