She'll move on to face world No. 1 Simona Halep, who needed three sets to defeat No. 12 Angelique Kerber. However, she stormed back to win the next two sets 6-3, 6-2 and get the win.
"I never gave up". "I missed a lot at the beginning of the match". "My head won it".
Muguruza holds a 3-1 career edge over Halep in head-to-head meetings but the Romanian won their only clash on clay in Stuttgart in 2015.
The victor of Thursday's semi-final will also decide the world number one spot which Muguruza held for four weeks previous year.
"I have just to stay strong, to try to make her uncomfortable on court and to try to play my game", Halep said. Sharapova had 27 unforced errors and had her serve broken six times.
Kerber, bidding to become the second German woman to reach the last four here, after Andrea Petkovic, since Steffi Graf in 1999, was visibly ailing because of blisters in the deciding set and the medical time out after three games didn't help her to solve the issue.
It is the first time that two American women have reached the last four at Roland Garros since 2002, when Serena Williams beat sister Venus in the final, after a semi-final win over Jennifer Capriati.More news: Intel's 28-Core 5GHz Processor And Test System Breaks Cover
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She also lost in the 2014 final to Maria Sharapova with Caroline Wozniacki denying her in the Australian Open final in January. Nadal was serving for the second set at 5-3, 30-15, when another shower came and action was halted for the day.
Halep is aware she can not afford another poor start on Thursday against 24-year-old Muguruza who has been tested just once in Paris and that was in the first round where fellow former victor Svetlana Kuznetsova pushed her to a tiebreak in the first set.
In the other men's quarterfinal, No 3 Marin Cilic and No 5 Juan Martin del Potro were at 5-5 in a first-set tiebreaker when the matchup of past US Open champions was stopped. Some of those matches were very defining for me.
By the time Sharapova recovered somewhat to play better it was too late, and Muguruza was into her impressive stride, with the court finally filling up post-lunch. Muguruza, the 2016 French Open champion, was world number one for four weeks from September 11 to October 8 a year ago.
"When you're writing an autobiography, I don't think there is any reason to write anything that's not true", said Sharapova after being knocked out of Roland Garros by Garbine Muguruza 6-2, 6-1 in the quarter-finals.
Halep has won five of her past nine matches against the 12th-seeded Kerber, including their most recent encounter in the Australian Open semifinals when she saved two match points.
"I think there are a lot of good things like the way my body has handled the long matches that I have played, the back-to-backs".