Narumi Katou is a middle-aged man afflicted with the peculiar ZONAPHA Syndrome: a rare and unexplained condition that triggers severe, random seizures in those who have it, with the sole remedy being the sight of someone laughing. One day, while working his part-time job, Narumi collides with a young boy carrying a massive suitcase who is fleeing from three adults. The boy introduces himself as Masaru Saiga, the new owner of the renowned Saiga Enterprises following his father's recent passing. However, other family members are attempting to assassinate him to seize the fortune for themselves. Determined to protect the child, Narumi assists Masaru in escaping and ends up battling the pursuers, only to find out they are sentient humanoid puppets possessing superhuman strength. Just as Narumi is on the verge of defeat, a white-haired girl suddenly enters the fight and quickly summons another puppet from the boy's suitcase, identifying herself as Shirogane, Masaru's guardian. Karakuri Circus follows three individuals from diverse backgrounds whose destinies intertwine and diverge as they uncover the secrets of an ancient story of love and betrayal, along with the long-standing, ancient conflict between humans and puppets.