Set in a dystopian future, humanity has retreated to massive fortress cities called Plantations to escape the threat of Klaxosaurs, mysterious creatures that emerge from the earth. Society is governed by the authoritarian APE organization, which enforces strict control over reproduction and human development. Children are raised in isolated facilities, devoid of familial bonds, and trained to pilot giant mechs known as Franxx in male-female pairs. These pilots, referred to as parasites, are essential for defending humanity against the Klaxosaurs.

The protagonist, Hiro, is a former prodigy who struggles to find his place after failing to synchronize with a Franxx. His life changes when he encounters Zero Two, a mysterious and rebellious pilot with horns and red skin, traits that mark her as non-human. Zero Two is infamous for her lethal partnership record, as her previous partners have died after three sorties. Despite the risks, Hiro forms a bond with her and becomes her new partner, earning the nickname "Darling." Together, they pilot the powerful Franxx unit, Strelizia, and join Squad 13, a group of young pilots stationed at Plantation 13.

Squad 13 consists of other pilot pairs, including the assertive leader Ichigo, the reserved Goro, the cheerful Mitsuru, the quiet Kokoro, the fiery Futoshi, the reserved Ikuno, and the energetic Zorome. As the story progresses, the squad faces increasingly dangerous Klaxosaur attacks while grappling with their own emotions, relationships, and the mysteries of their world. Hiro and Zero Two's partnership becomes central to the narrative, as their connection challenges the rigid societal norms imposed by APE.

The plot delves into the origins of the Klaxosaurs, the true nature of Zero Two, and the hidden agenda of APE. It is revealed that the Klaxosaurs are ancient beings defending the planet, while APE seeks to exploit the planet's resources for their own ends. Zero Two's hybrid nature ties her to both humanity and the Klaxosaurs, creating internal conflict as she struggles with her identity and her desire to become fully human. The story explores themes of identity, freedom, and the consequences of humanity's exploitation of the planet.

As the conflict escalates, Squad 13 uncovers the truth about their world and the sacrifices required to protect it. The narrative culminates in a climactic battle that forces the characters to confront their destinies and the cost of their choices. The series concludes with a bittersweet resolution, emphasizing the enduring impact of human connection and the resilience of the human spirit in the face of adversity.