FLCL is a coming-of-age story and revolves around Naota Nandaba, a 12-year-old, working-class boy living with his widowed father and grandfather. His life in the city of Mabase is interrupted by the arrival of Haruko Haruhara, who runs over Naota with her yellow Vespa 180 SS scooter, gives him CPR, then hits him on the head with a blue vintage Rickenbacker 4001 left-handed electric bass guitar.
Naota discovers that the blow to his head created an "N.O." portal, from which giant robots produced by a company known as Medical Mechanica emerge periodically. The first of these robots is hit on the head by Haruko and turns friendly to Naota and his family, doing menial tasks for the family throughout the series, and is later named Canti.
Naota later finds Haruko working in his house as a live-in maid. It is later discovered that Haruko is an investigator for the Galactic Space Police Brotherhood. Haruko uses Naota for her search for the Pirate King, Atomsk. She is at odds with Medical Mechanica, a monolithic industrial corporation. Naota is being watched by Commander Amarao, a special agent of the Bureau of Interstellar Immigration, who believes that Medical Mechanica is out to conquer the galaxy.
Medical Mechanica sends three robots through the portal in Naota's head, which he, Haruko, and Canti fight off. In the series finale Medical Mechanica succeed in turning on a world ending device, helped when Haruko combines Naota, Canti, and a device called the Terminal Core. As it turns out, Atomsk was hiding in Canti, and Naota is able to temporarily absorb his powers when they're combined. After stopping the world ending device and briefly fighting Haruko, Atomsk leaves Naota's body and leaves the planet.
Haruko then leaves the planet once again, presumably still chasing after Atomsk on her Vespa, which is also shown to be able to fly. The city has resumed it's normal day-to-day operation, and Naota is shown in a new uniform walking to school with his classmates.
