The 12-time grand slam victor, who equalled Jimmy Connors' mark of 233 triumphs in grand slam singles matches, has not found progress at Roland Garros particularly easy and now faces sixth seed Dominic Thiem in the semi-finals.
Djokovic also crushed Thiem in the semifinals past year in Paris.
The No.2-seed converted 7 of 10 break points and smashed 34 winners to ensure a finish just before sunset in Paris. "Then maybe change something up and hope I play a good match".
He'll next face Austrian Dominic Thiem, who blitzed Horacio Zeballos, 6-1, 6-3, 6-1, to reach his second consecutive quarterfinal.
Austria's Dominic Thiem clenches his fist as he plays Serbia's Novak Djokovic during their quarterfinal match the French Open tennis tournament at the Roland Garros stadium, Wednesday, June 7, 2017 in Paris.
"I'm sad. It's a very painful defeat here in the French Open", said Muguruza, who left Court Suzanne Lenglen angrily wagging her finger at the crowd. In the women's section, former World No. 1 Caroline Wozniacki and French No. 1 Kristina Mladenovic play their quarter-final games today against Latvian Jelena Ostapenko and former French Open semi-finalist Timea Bacsinszky, respectively.
Nadal remains on course to meet second seed Novak Djokovic in the last four after the defending champion defeated Albert Ramos-Vinolas 7-6 (7-5), 6-1, 6-3.
The clay courts of Roland Garros host the second Grand Slam of the season.
It's Djokovic's eighth straight trip to the quarterfinals at Roland Garros as he seeks to repeat as champion.
If Nadal and Djokovic prevail in their Round of 8 matches, tennis fans will be treated to a blockbuster semi-final clash against the two modern-day greats on Thursday.
Djokovic leads the head-to-head series 5-0 and will once again be the clear favorite.
Croatian qualifier Petra Martic upset 17th-seeded Anastasija Sevastova 6-1 6-1 to reach the fourth round of the French Open.
Round 3: Veronica Cepede Royg (Par) bt Mariana Duque (Col) 3-6, 7-6 (2), 6-3; 5-Elina Svitolina (Ukr) bt Magda Linette (Pol) 6-4, 7-5; 2-Karolina Pliskova (Cze) bt Carina Witthoeft (Ger) 7-5, 6-1; Petra Martic (Cro) bt 17-Anastasija Sevastova (Lat) 6-1, 6-1.
The rain delay suited Kei Nishikori as he recovered to beat Hyeon Chung 7-5, 6-4, 6-7 (4), 0-6, 6-4 when their third round match resumed at the French Open.
Ramos-Vinolas' resistance in a 73-minute opening set, where Djokovic had his serve broken twice to trail 4-2 before fighting back to win the tie-breaker, indicated it could be another battle for the Serb.