Living underground in Giha Village, Simon and Kamina dream of a life on the surface. When their home is invaded from above, it is up to them to activate the mysterious mecha Lagann and save their village.

Now that they've made it to the surface, Simon and Kamina must join together with Yoko and her village to defeat the Beastmen pursuing them.

Having temporarily stalled Viral and Thymilph in the last skirmish, the Team Gurren and their newly arrived allies join forces as "Team Dai-Gurren" and launch a decisive strike against the regrouping Gunmen force.

Team Dai-Gurren managed to take control of the enemy fortress, but is still mourning the death of one of their own, especially Simon. After falling off a cliff, he notices a Gunman throw a capsule into a deep valley. Simon inspects it and finds he is able to open it with the same drill key he uses to pilot Lagann, and inside is a young human girl named Nia, but their introduction is cut short when an enemy Gunman appears.

Team Dai-Gurren are now on their way to Beastmen's capital city, Teppelin but there's a vast ocean in their way. The only way for them to get across is for the Dai-Gurren to be modified, so while they wait everyone goes to chill out at the beach. Once preparations are complete, the Great Gurren Brigade begins their cruise, but there's an ambush waiting for them.

At last, Team Dai-Gurren arrives at the outskirts of Teppelin, but before aiming to the city, they must face a combined full-scale attack of Cytomander and Guame's forces.

The last of the Divine Generals fall, and the city of Teppelin collapses, revealing a Gunman of gigantic proportions. Simon and Nia struggle to pass through it in order to confront her father, the Spiral King himself.

One year earlier, Yoko starts working as a schoolteacher on an island until she learns of the situation at Teppelin and returns to break Simon free. Once again reunited, Simon and the members of Team Dai-Gurren launch themselves into space to protect the Arc-Gurren from the enemy forces, now accompanied by Viral as co-pilot of the Gurren-Lagann.

The Gurren-Lagann and the Arc-Gurren join together to form the massive Arc-Gurren-Lagann and stop the Human Annihilation System.

After finally transforming their flagship into the Super Galactic Gurren-Lagann, Simon and his friends successfully fight back against the enemy. When their enemy starts to use their own memories and desires against them, Kamina reappears to help.