Gundam SEED Destiny sets the story two years after the original series and it starts when the leader from Orb, Cagalli Yula Athha, reunites with PLANT's chairman Gilbert Durandal to discuss the construction of new mobile suits made for the military organization ZAFT. Three of them are stolen by a group called Phantom Pain, which is controlled by the Blue Cosmos terrorist organization. Cagalli's bodyguard Athrun Zala joins ZAFT pilot Shinn Asuka to stop them.^[1] During the fight, ZAFT's battleship Minerva is ordered to destroy the ruins of a space colony to prevent it from crashing into Earth. They find out that rogue ZAFT soldiers are controlling the colony in order to crash it into Earth.^[1] After failing to completely destroy the colony, a second war starts between the factions, the Earth Alliance and ZAFT, once news has spread that ZAFT soldiers caused the colony to collide on Earth. The neutral country of Orb allies with the Earth Alliance, with the former having also joined Blue Cosmos. This leads these three faction to confront the ZAFT soldiers several times, with Athrun having returned there.

Later in the war, the Archangel class assault ship interferes in the fights between ZAFT and the Earth Alliance's faction. Allied with the Archangel, Cagalli fails to stop her country from fighting and the Archangel is involved in the fight. Athrun becomes disaffected after Gilbert Durandal orders the destruction of his friend Kira Yamato and the Archangel, deeming them as enemies. He defects with Meyrin Hawke when Durandal frames him as a traitor. Cagalli is able to regain leadership from Orb, causing the Blue Cosmos' members to defect to space. The leader of Blue Cosmos, Lord Djibril, orders the weapon Requiem to be fired which destroys many of the space colonies of PLANT, resulting in many deaths. The crew of the Minerva successfully kills Lord Djibril and capture the Requiem. Gilbert Durandal then announces the "Destiny Plan", a plan where a person's job or task will be based on their genetics, and uses the Requiem to destroy anyone who opposes him. This brings Shinn and the crew of the Minerva into direct conflict with the Archangel ship and the ZAFT forces opposing. Kira and Athrun with their new mobile suits ZGMF-X20A Strike Freedom and ZGMF-X19A Infinite Justice respectively and their allies, defeat the ZAFT forces and destroy the Requiem. Durandal is killed by one of his own followers, Rey Za Burrel.

The series' ending was expanded in both the original video animation and the last compilation film.^[2] Soon after Durandal's death, the Earth Alliance, ZAFT, and the Orb Union meet to end the war, with Lacus Clyne acting as the negotiator. After fighting between each other various time in their mobile suits, Kira and Shinn meet in person for the first time and promise to join forces for a better future.