"Mobile Suit Gundam Seed Destiny" is a direct sequel to "Mobile Suit Gundam Seed," set in the Cosmic Era timeline. The story begins two years after the conclusion of the first series, with the Earth Alliance and the PLANTs, a nation of genetically enhanced Coordinators, maintaining a fragile peace. The narrative primarily follows Shinn Asuka, a young Coordinator and soldier of ZAFT (Zodiac Alliance of Freedom Treaty), who harbors deep resentment toward the Earth Alliance after losing his family during the previous war. Shinn pilots the Impulse Gundam, a cutting-edge mobile suit, and becomes a key figure in ZAFT's efforts to maintain order and protect the PLANTs.

The plot intensifies when ZAFT's leader, Gilbert Durandal, unveils the Destiny Plan, a controversial initiative aimed at restructuring society by assigning individuals roles based on their genetic predispositions. This plan sparks conflict, as it is seen as a threat to free will by many, including the Orb Union, a neutral nation led by Cagalli Yula Athha. Cagalli, alongside her allies, including the returning protagonist Kira Yamato, opposes Durandal's vision. Kira, now piloting the Strike Freedom Gundam, re-enters the conflict to protect his ideals of peace and coexistence between Coordinators and Naturals (non-enhanced humans).

The story explores themes of war, identity, and the ethical implications of genetic engineering. Key characters include Athrun Zala, a former ZAFT soldier torn between loyalty to his nation and his personal convictions, and Lunamaria Hawke, a ZAFT pilot who becomes entangled in the shifting allegiances of the war. The narrative is marked by intense mobile suit battles, political intrigue, and moral dilemmas as factions clash over the future of humanity. The series culminates in a climactic confrontation that determines the fate of the Destiny Plan and the balance of power in the Cosmic Era.