In a dystopian future, humanity has abandoned the Earth's surface, retreating to massive, mobile fortress cities called Plantations. Society is structured around the survival of the species, with children raised in isolated facilities and trained to pilot giant mechs known as Franxx. These mechs are co-piloted by pairs of male and female pilots, referred to as "stamens" and "pistils," respectively. The Franxx are humanity's primary defense against monstrous creatures called Klaxosaurs, which threaten the remnants of civilization.

The story centers on Hiro, a former prodigy who struggles to find a partner after failing to synchronize with multiple pistils. His life changes when he encounters Zero Two, a mysterious and enigmatic girl with red horns and a reputation as a dangerous pilot. Zero Two is a hybrid, part-human and part-Klaxosaur, and her unique biology makes her both feared and revered. Despite warnings about her lethality, Hiro forms a bond with Zero Two, becoming her stamen and piloting the Franxx unit known as Strelizia. Their partnership earns them the codename "Darling in the Franxx."

As Hiro and Zero Two fight alongside their squad, Squad 13, tensions arise within the group. The pilots, including the assertive Ichigo, the reserved Goro, the cheerful Miku, the reserved Zorome, the shy Kokoro, the reserved Futoshi, and the quiet Ikuno, grapple with their roles in a society that suppresses individuality and emotions. The series explores their growing awareness of the world beyond their training, as they begin to question the rigid systems governing their lives.

The narrative delves into the origins of the Klaxosaurs and the true nature of humanity's struggle. It is revealed that the Klaxosaurs are ancient beings defending the Earth from human exploitation, while the adults in power have sacrificed their humanity to extend their lifespans, relying on the children to fight their battles. The Franxx pilots uncover the existence of APE, a shadowy organization controlling society, and learn about the experiments that created Zero Two and other hybrids.

As the conflict escalates, Hiro and Zero Two's relationship becomes central to the story. Zero Two's desire to become fully human and Hiro's determination to protect her drive much of the narrative. The series culminates in a climactic battle against the Klaxosaur Princess, a powerful entity leading the Klaxosaurs, and the revelation of a larger cosmic threat. The final arc sees humanity and the Klaxosaurs joining forces to confront this existential danger, with Hiro and Zero Two making a profound sacrifice to ensure the survival of both species.

The series blends themes of identity, love, and rebellion against oppressive systems, set against a backdrop of mecha action and post-apocalyptic intrigue. The characters' emotional journeys and the evolving dynamics within Squad 13 provide a human core to the high-stakes narrative, making "DARLING in the FRANKXX" a story that intertwines personal growth with epic, world-altering events.