Nazo no Murasme-jō takes place in the Edo period Japan. One stormy night, the grand Murasame Castle is attacked by aliens, and a giant statue known as Murasame comes alive. The alien used their power to take control of four nearby castles and their four daimyo using four powerful orbs. The leaders then use the orbs to summon ninja and other evil creatures that attack the people in the land. To protect the land, the shogun sends Takamaru on a mission to infiltrate the castle and bring peace back to the land.
Takamaru traveled through the land and the four castles, killing the four daimyo and destroying the orbs on his way. He also rescued the daughters of the daimyo in the castles before he finally reached the Murasame Castle. After making his way through the by now totally twisted castle, Takamaru challenged the Murasame Statue. Destroying it revealed a path to the aliens' world where he once for all destroyed the alien.