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.

Thymilph, one of the Four Divine Generals of the mysterious Spiral King, arrives to support Viral's Enki, with the massive mobile Gunmen fortress, the Dai-Ganzan. Kamina and Simon pilot the Gurren-Lagann against seemingly overwhelming odds.

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.

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.

The members of Team Dai-Gurren make their preparations for the imminent war against the Anti-Spirals, but Rossiu is missing. However, when Kinon tells Simon about what he really intends to do, both start to look desperately for him.

Guided by Simon and Nia's feelings for each other, Team Dai-Gurren break through dimensions in search for the Anti-Spirals' homeworld. But after falling into the enemy's trap, they end up losing some of their most precious members, due to its vicious offensive.