In the dystopian city-state of No. 6, a seemingly utopian society thrives under strict control and surveillance. Shion, a privileged elite resident, lives a sheltered life until the age of 12, when he encounters a fugitive named Nezumi during a storm. Defying the city's laws, Shion shelters Nezumi for the night, an act of rebellion that alters the course of his life. Four years later, Shion's world unravels when he is demoted from his elite status after being implicated in a mysterious incident involving parasitic wasps. Stripped of his privileges, he is forced to live in the city's outskirts, where he begins to question the true nature of No. 6 and its oppressive regime.

Reuniting with Nezumi, who now lives in the underground ruins outside the city, Shion learns the dark truths behind No. 6's facade of perfection. The city's authorities conduct inhumane experiments on its citizens, using them as test subjects to maintain control and suppress dissent. As Shion and Nezumi investigate further, they uncover a conspiracy involving the parasitic wasps, which are engineered to manipulate and control human behavior. Their journey exposes the corruption and brutality of the ruling class, as well as the suffering of those deemed expendable by the system.

The relationship between Shion and Nezumi evolves from mutual distrust to a deep bond as they navigate the dangers of their mission. Shion's idealism and compassion contrast with Nezumi's cynicism and survivalist instincts, creating a dynamic partnership. Supporting characters, such as Safu, Shion's childhood friend, and Dogkeeper, a resourceful ally, play pivotal roles in their fight against the city's tyranny. The narrative explores themes of freedom, identity, and the cost of resistance, culminating in a climactic confrontation that challenges the foundations of No. 6 and its inhabitants' futures.

The series balances its dystopian setting with moments of introspection and emotional depth, focusing on the characters' growth and the moral dilemmas they face. Through its exploration of societal control and individual agency, "No. 6" presents a thought-provoking narrative that resonates with themes of rebellion and human connection.