Mizuki, whose real name was Shigeru Mura, was hospitalised in early November after he collapsed in Tokyo, the office said on its website.
He underwent surgery but died this morning of multiple organ failure in hospital, it said.
The native of Tottori prefecture in western Japan began his career as a cartoonist after surviving World War II during which the conscripted Japanese soldier lost his left arm in a US air strike.
His works also covered the horror of war based on his battlefield experiences in New Britain island, now part of Papua New Guinea, and the harsh treatment common soldiers received from their superior officers.
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"You were never allowed to retreat (from) the front, you had to stay until you died," he told AFP in an interview earlier this year.
Rank and file soldiers were treated "not as human beings, but were thought to be something less than horses".
The area displays more than 100 statues of his cartoon characters and has attracted tourists and fans from across the country.
Mizuki received the Heritage Essential Award of the Angouleme International Comics Festival in France in 2009.