With victories over Svetlana Kuznetsova and Sam Stosure under her belt, it was the turn of Sharapova to experience the extreme might of the reigning Wimbledon champion, who eased to a 6-2 6-1 win in just 70 minutes.
That semi-final will also decide the number one spot next week.
A second and third break followed after more effortless power from the Spaniard and she is now just two wins away from her third major title.
Sharapova, playing at Roland Garros for the first time since 2015, suffered her most one-sided defeat at the Slams since a 6-3, 6-0 loss to Victoria Azarenka in the 2012 Australian Open final.
Sharapova, who missed the 2016 tournament because of a doping ban and past year after she was refused a wild card, was broken six times, committed 27 unforced errors and won just five points on her own serve in the second set.
Sharapova never really got going after double-faulting three times in the opening game on Court Philippe Chatrier, losing to third seed Muguruza to the first time in their four encounters.
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It was just her fifth loss in 25 Grand Slam quarter-finals.
In theory, Muguruza goes into today's match as favourite - certainly her seeding of No. 3 far outstrips Sharapova's No. 28 - but it feels like a tricky one to call. Muguruza sensed weakness and pounced for a 4-0 lead.
An anti-climactic match ended predictably, with a Sharapova backhand nestling in the net - her 27th unforced error.