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.
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 their fallen comrade, 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.
Having been temporarily spared by Adiane, another of the Four Divine Generals, Team Dai-Gurren uses the reprieve to reassess their situation. Nia learns of Kamina's significance in Simon's erratic behavior and offers him some stinging, yet honest advice, which draws the ire of an untrusting Yoko. With tension building within the Team, the crew scrambles to stand by Nia's side when Adiane returns to complete her stalled attack.
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' home world. But after falling into the enemy's trap, they end up losing some of their most precious members, due to its vicious offensive.
Team Dai-Gurren struggles to escape from the ocean of despair created by the Anti-Spirals without success, until history repeats itself, as another irreplaceable member of the Team sacrifices himself to save the others.
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, someone reappears to help.
At last, Simon and Nia are reunited, and by combining the power of its members, Team Dai-Gurren creates the galaxy-sized Tengen Toppa Gurren-Lagann, and engage the Anti-Spiral threat in a decisive battle to determine the fate of the universe.
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