The story revolves around Mahiro Fuwa, a teenager whose family was mysteriously murdered one year before and his friend Yoshino Takigawa. Mahiro is contacted by Hakase Kusaribe, the leader of the Kusaribe clan who was left stranded on an unknown desert island by her followers, and agrees to help Hakase in exchange of her help to find out the culprit for the death of his family. Upon learning of his friend's intentions, Yoshino joins him on his quest to stand against the Kusaribe clan who intends to awake the "Tree of Zetsuen" whose power can bring ruin to the entire world. 

Several dialogues and plot elements in Zetsuen no Tempest pay homage to the works of William Shakespeare.