Gurren Lagann takes place in a fictional future where Earth is ruled by the Spiral King, Lord Genome, who forces mankind to live in isolated subterranean villages that have no contact with the surface world or other villages. These villages are under constant threat of earthquakes, so select villagers called diggers are relegated to expand their homes deeper underground. Simon, a meek young digger who is ostracized by his peers, finds solace in his best friend and older brother figure, an eccentric delinquent named Kamina, who 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 Gunman. Shortly thereafter, a giant Gunman crashes through the ceiling and begins attacking the village, followed by a girl named Yoko who attempts to repel the Gunman. Simon uses his Core Drill to activate the smaller Gunman, which Kamina names Lagann and is used to destroy the larger Gunman and break through to the surface world.
Simon and Kamina learn from Yoko that humans on the surface world are attacked each day by Gunmen piloted by beastmen, humanoid creatures who serve as Lord Genome’s army. Kamina hijacks a Gunman 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 is eventually renamed Team Dai-Gurren. Eventually Team Dai-Gurren captures an enemy Gunmen fortress to use as their base of operations, though Kamina is mortally wounded in the preceding battle.
Simon sinks into depression following Kamina’s death when he meets Nia, Lord Genome’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 Lord Genome and the beastman army.
Seven years later, mankind has prospered on the surface world with Simon and the members of Team Dai-Gurren serving as the world’s government. This attracts the attention of a new threat called the Anti-Spirals, who use Nia as their messenger to announce the Moon’s collision with Earth, which will wipe out all life on the planet. With guidance from a partially resurrected Lord Genome, Team Dai-Gurren prevents the moon’s collision, rescue Nia, and destroy 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 ensure the safety of the universe.