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.

Nia true identity is revealed, as she flaunts her authority to get rid of another one of the Four Divine Generals, Adiane. The members of the Great Gurren Brigade are now suspicious of Nia and her true intentions, but she is only concerned about the depressed Simon. Adiane later returns to finish them all off, with Lordgenome's blessing.

Trying to do her part in Team Dai-Gurren, Nia decides to become a cook, but just before the crew have a taste of her dishes, Cytomander, the fourth member of the Divine Generals, launches an aerial attack on the Dai-Gurren. Simon leads the counter-attack on the Gurren-Lagann, this time accompanied by Yoko, who replaces a sick Rossiu.

During the following seven years, a new civilization rises and prospers under Simon's leadership. However, these peaceful times come to end when the threat mentioned in Lordgenome's last words starts to reveal itself.

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.

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.