Mitsukuri was born in Edo (present-day Tokyo) to a noted family of scholars working for the Tokugawa bakufu. He studied "rangaku" and received a posting to the "Bansho Shirabesho," the Shōgun's research institute for foreign technology. In 1867, he was selected to accompany the Shogunate's expedition to the Paris World Exposition, which proved to be an eye-opener.