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Muguruza won at Roland Garros in 2016 and also won last year’s WTA final.
However, in Sunday’s match of the first round the 10th racket of the world fell to the unsown Kanepi.
Muguruza, seeded 10th, lost 2-6 6-3 6-4 to Estonia’s 46th racket, recording its 10th career victory at the Major over the top 10 player. .
Kanepi, who is the oldest player in the women’s core network, has also broken her brilliant record against seeded Grand Slam tournaments, now winning 19 such matches.
Among the active players only Serena Williams (29), her sister Venus (22) and 10th seeded Victoria Azarenka (21) have more such victories.
Now she will play in the second round with Brazilian Beatrice Hadad Maya.