In a dystopian, post-apocalyptic future, Earth has become a desolate wasteland due to humanity's intensive extraction of magmatic energy. To survive, society has isolated itself in gigantic, fortified mobile cities called Plantations, where adults live immortal, yet emotionless lives under the command of an authoritarian leadership known as APE or "Daddy." The greatest threat to this existence are the Klaxosaurs, gigantic creatures attracted to the same energy that humans consume. To combat them, children are artificially created in laboratories, deprived of names and knowledge of the outside world, serving strictly as "parasites" created to pilot the Franxx—giant robots that require perfect neural and emotional synchronization between a boy (stamen) and a girl (pistil).

The plot follows Hiro, a young pilot who was once a prodigy but has lost the ability to synchronize with his partners, becoming useless to the system. His reality changes drastically when he meets Zero Two, an elite pilot with horns and Klaxosaur blood, known for her lethal reputation of draining the life force of her partners after three flights. When they team up in the Franxx called Strelizia, Hiro discovers that he is the only one capable of piloting with her without dying. As the squad of young people faces brutal battles and begins to live more independently, the children begin to discover previously forbidden human feelings, such as love, reproduction, and individuality. The bond between Hiro and Zero Two gradually reveals dark secrets about their past, the true and terrifying nature of the Klaxosaurs, and the real intentions of humanity's leaders, culminating in a battle of cosmic proportions for the fate of Earth.