"Zettai Karen Children" is set in a world where individuals with psychic abilities, known as espers, are monitored and controlled by organizations to prevent misuse of their powers. The story centers on three young girls—Kaoru Akashi, Aoi Nogami, and Shiho Sannomiya—who possess extraordinary psychic abilities and are classified as Level 7 espers, the highest rank. These children are recruited by the government-affiliated organization BABEL, which aims to train and utilize their powers for the greater good.

The trio forms "The Children," a special unit tasked with handling missions involving other espers or supernatural threats. Kaoru, the group's leader, wields telekinesis and is known for her strong sense of justice. Aoi, the most reserved of the three, specializes in teleportation and precognition, while Shiho, the most aggressive, uses pyrokinesis and often clashes with authority figures. Their handler, Kyousuke Hyoubu, is a former esper who initially mentors them but later becomes a complex antagonist due to his disillusionment with BABEL's methods and his own hidden agenda.

The narrative explores the ethical dilemmas surrounding the use of psychic powers, the exploitation of espers, and the balance between personal freedom and societal safety. As the story progresses, the girls face increasingly dangerous missions, uncovering secrets about BABEL and the origins of their powers. The series also delves into the personal struggles of the characters, particularly Kaoru's determination to protect her friends and Shiho's internal conflict between her aggressive tendencies and her loyalty to the group.

Kyousuke Hyoubu's role evolves significantly throughout the series, as his past and motivations are revealed. His organization, PANDRA, opposes BABEL and seeks to liberate espers from government control, creating a moral gray area that challenges the protagonists' beliefs. The dynamic between The Children and Hyoubu becomes a central focus, blending action, emotional depth, and philosophical questions about power and responsibility.

The series balances episodic missions with an overarching plot, gradually building tension as the characters confront external threats and internal conflicts. Themes of friendship, trust, and the consequences of wielding immense power are woven into the narrative, making "Zettai Karen Children" a compelling exploration of psychic abilities and their impact on individuals and society.