Tengen Toppa Gurren Lagann takes place in a fictional far future where human beings have been forced underground and thrive in isolated subterranean civilizations. These "villages" have no contact with the surface world nor other villages. Since frequent earthquakes damage infrastructure, the villages must constantly expand deeper into the earth — individuals designated to this task are known as "diggers".
Jiiha Village is the home of Simon, a fourteen year old digger who was orphaned when his parents were killed in an earthquake. He is respected by the village elder as the best of the diggers, but is ostracized by his peers. After discovering a special drill key deep in the ground, he is recruited by an eccentric fellow orphan named Kamina into his group, the "Gurren Brigade". Kamina dreams of the surface world, which he visited as a child with his father but had to return home because he was too weak to survive.
After a failed attempt at reaching the surface, Kamina is jailed by the elder and Simon resumes digging, only to discover "a big face" deep in his tunnel. As he excitedly fetches Kamina to show him the discovery, he is caught by the village elder, but Kamina's punishment is interrupted by the ceiling of Jiiha Village collapsing as an enormous robot falls into the cavern. A fourteen year old girl named Yoko appears and tries to fight the robot with a large rifle, but initially cannot do much. Simon takes Kamina and Yoko to the "big face" he found earlier and discovers that the small drill key can be used to activate the small robot which he uses to end up destroying the much larger robot and effectively break through to the surface.
It is on the surface that Simon and Kamina discover that there are more large robots known as Gunmen piloted by "Beastmen" that terrorize the surface dwellers during the day. Simon and Kamina help Yoko and her village destroy three more Gunmen and Kamina takes one for himself, naming it Gurren. Eventually, Simon and Kamina decide that they will go on a journey to end the constant struggle between Beastmen and humans. Simon and Kamina are initially accompanied by Yoko and a mechanic from Yoko's village named Leeron as they head out to find the Beastmen's Human Eradication Army main head-quarters.