Gurren Lagann takes place in a fictional future where Earth is ruled by the Spiral King, Lordgenome, who forces mankind to live in isolated subterranean villages. These villages have no contact with the surface world or other villages, and are under constant threat of earthquakes. Select villagers called diggers are conscripted to expand their homes deeper underground. Simon, a meek young digger ostracized by his peers, finds solace in his best friend and older brother figure, an eccentric delinquent named Kamina. Kamina allows Simon to join his gang, Team Gurren, to help him achieve his dream of visiting the surface world. One day, Simon unearths a drill-shaped key called a Core Drill, followed by a small mecha resembling a face called a Gunmen. Shortly thereafter, a giant Gunmen crashes through the ceiling and begins attacking the village, followed by a girl named Yoko who attempts to repel the Gunmen. Simon uses his Core Drill to activate the smaller Gunmen, which Kamina names Lagann and is used to destroy the larger Gunmen and break through to the surface world.
Simon and Kamina learn from Yoko that humans on the surface are attacked each day by Gunmen piloted by beastmen, humanoid creatures who serve as Lordgenome’s army. Kamina hijacks a Gunmen and names it Gurren, combining it with Simon’s Lagann to form the mecha Gurren Lagann. Their actions inspire other humans to steal their own Gunmen and join Team Gurren, which Kamina renames Team Dai-Gurren. Eventually Team Dai-Gurren captures an enemy Gunmen fortress to use as their base of operations, though Kamina is killed in the preceding battle. Simon sinks into depression following Kamina’s death when he meets Nia, Lordgenome’s daughter. Team Dai-Gurren is initially distrustful of her, but allows her to join when it becomes apparent that she was abandoned by her father. Nia helps Simon come to terms with Kamina’s death, and he takes up the role as Team Dai-Gurren’s leader, leading them to defeat Lordgenome and the Beastman army.
Over the next seven years, mankind prospers on the surface world with Simon and the members of Team Dai-Gurren serving as the world’s government. As soon as the world’s population reaches one million people, an alien race called the Anti-Spirals emerges and uses Nia to announce the moon’s collision with Earth, which will wipe out all life on the planet and prevent them from evolving to such an extent that they will risk destroying the universe in a cataclysmic event called the Spiral Nemesis. With guidance from a resurrected Lordgenome, who had hidden mankind underground to protect them from the Anti-Spirals, Team Dai-Gurren prevents the moon’s collision, rescues Nia, and destroys the Anti-Spirals. This, however, causes Nia to fade away and die as her own existence is tied to that of the Anti-Spirals. Simon spends the rest of his life wandering the planet as a nameless vagrant while his comrades set out to contact other races throughout the galaxy to help prevent the Spiral Nemesis and ensure the safety of the universe.