The Orb Union space colony, Heliopolis, is attacked by ZAFT, despite its neutrality since the beginning of the Bloody Valentine War. Kira Yamato accidentally sees the Earth Alliance's new prototype mobile suits, which have been secretly constructed at the Heliopolis Morgenroete factory. He encounters his childhood friend, Athrun Zala, now a ZAFT soldier as one of the attackers.

ZAFT is able to steal four of the five G-Project prototype mobile suits, leaving only the GAT-X105 Strike. With Murrue Ramius unable to pilot it effectively, Kira pilots the Strike and defends Heliopolis against the invading ZAFT forces to protect his friends. Ensign Natarle Badgiruel takes command of the new mobile assault ship Archangel with the surviving crew members.

Lt. Murrue Ramius takes over as captain of the Archangel and Kira and his friends are detained for seeing top secret military weapons. Rau Le Creuset is determined to capture the Strike after seeing how well it moved and sends out mobile suits to retrieve it. Disobeying orders, Athrun also dispatches so he could confirm if Kira is the one piloting the Strike, but when he finds his answer, Heliopolis crumbles as it sustains too much damage.

Kira discovers a malfunctioning lifeboat and brings it aboard the Archangel. Everyone is surprised to find Flay Allster as one of the rescued civilians. The Archangel decides to head for the Eurasian Federation military satellite Artemis to seek help. Rau Le Creuset follows and plans an attack on the Archangel. Kira decides to continue piloting the Strike and his friends volunteer to become members of the Archangel crew as his support.

Mu La Flaga and Kira launch a counteroffensive against the ZAFT ship Vesalius. The Strike's Phase Shift Armor runs out of power in the middle of the battle and Athrun uses this moment to grab the Strike so he can take Kira with him, but Kira frees himself with Mu's help.

The Archangel and its crew are held captive by the Artemis forces. Nicol Amalfi in his GAT-X207 Blitz attacks Artemis, using its Mirage Colloid armor to remain effectively invisible and destroys the Umbrella of Artemis, which protects the asteroid fortress. During the attack, the Archangel is able to escape.

The Archangel forages for water in the Debris Belt. They are shocked to find themselves in the ruins of Junius Seven, so the crew decides to hold a memorial. As they are excavating ice found around the ruin, a ZAFT mobile suit attacks, but Kira dispatches him. Kira finds a floating lifepod and takes it aboard.

Lacus Clyne, the daughter of PLANT Supreme Council Chairman Siegel Clyne, is found within the lifepod. Her presence causes tension within the crew, but when the crew receives a message from the 8th Fleet that they are being searched and rescued, they are overjoyed.

The Archangel is to meet with the 8th fleet but is attacked by the Le Creuset Team. Flay witnesses the death of her father when Kira fails to protect the escort ships. In desperation, the Archangel reveals Lacus is on board the ship, causing the attackers to withdraw.

With everything that has happened, Kira becomes depressed. He is comforted by Lacus, who is strolling around the ship without permission. Kira returns Lacus to Athrun against orders, but refuses Athrun's invitation to change sides.

Le Creuset launches an attack on the Archangel. Kira's desire to protect his friends awakens an unknown almost berserker ability. He single-handedly defeats the attacking GAT-X207 Blitz, GAT-X103 Buster, and GAT-X102 Duel.

Kira and his friends are given permission to leave the Archangel, but after overcoming the initial shock of her father's death, Flay decides to enlist in the Earth Alliance Forces, prompting Sai Argyle, Kuzzey Buskirk, Miriallia Haw, and Tolle Koenig to do the same. Kira stays on board the as well to continue protecting his friends. The Duel is upgraded with an Assault Shroud.

Le Creuset attacks once again as the Archangel and the 8th Fleet approaches Earth. The Archangel is able to descend to Earth, but not without the loss of the entire 8th Fleet. Yzak Joule, the pilot of the Duel, vents his frustration by destroying a spacecraft carrying Heliopolis refugees that Kira had rescued previously.

It's now C.E. 73 and three of ZAFT's newest mobile suits are stolen. During the highjacking, Cagalli, now Orb's head of state, and Athrun, now her bodyguard, are meeting with ZAFT's new head honcho.

The Archangel and its allies are now humanity's last hope to prevent Durandal from carrying out his Destiny Plan. Once again, a fierce battle begins around the Requiem cannon and its relay stations, and the Gundam pilots meet in a final confrontation over the lunar surface. Shinn against Athrun, Kira against Rey, Archangel against Minerva... In the end, there can be only one victor.

Extended cut of SEED Destiny's series finale released as an OVA.