The 12th-seeded Simon was blown away on a windswept court Suzanne Lenglen as 2014 Australian Open champion Wawrinka sprayed the court with winners despite the damp conditions making the clay court slower.
Wawrinka, who spurred Switzerland to Davis Cup glory with victory over France on clay last November, ended the lopsided contest on his first match point when Simon sent a shot long.
Wawrinka will next face 17-times grand slam champion Roger Federer, or another Frenchman, 13th seed Gael Monfils.
(Reporting by Julien Pretot; Editing by Pritha Sarkar)
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