"No. 6" is a dystopian science fiction manga series set in a futuristic city-state of the same name, which is portrayed as a utopia for its elite citizens. The narrative begins with Shion, a privileged 12-year-old boy living in the affluent Chronos district of No. 6. One stormy night, Shion shelters a fugitive named Nezumi, who escapes from the city's correctional facility. This act of kindness leads to Shion's fall from grace, as he is stripped of his privileges and relocated to the lower-class areas of the city.

Four years later, Shion works as a park maintenance worker and uncovers a series of mysterious deaths linked to parasitic wasps. His investigation reunites him with Nezumi, now a cynical and resourceful young man living outside the city. Together, they delve deeper into the dark secrets of No. 6, uncovering its oppressive regime, unethical experiments, and the exploitation of its citizens. The story explores themes of freedom, identity, and the consequences of blind obedience to authority.

Shion and Nezumi form a complex relationship, balancing trust and tension as they navigate the dangers of their mission. Shion's idealism and scientific curiosity contrast with Nezumi's pragmatism and distrust of the system. Supporting characters include Safu, Shion's childhood friend, who becomes a key figure in the resistance against No. 6, and Dogkeeper and Inukashi, who assist the protagonists in their journey. The narrative builds toward a climactic confrontation with the city's rulers, revealing the true nature of No. 6's control over its inhabitants and the sacrifices required to dismantle its oppressive structures. The series concludes with a resolution that leaves room for interpretation, emphasizing the ongoing struggle for freedom and the resilience of the human spirit.