The series is the first of the Gundam franchise set in the "Cosmic Era" in which mankind is divided between normal Earth dwelling humans, known as "Naturals", and the genetically altered humans known as "Coordinators", who live in space colonies. The nations of mankind are loosely aligned into three factions. The natural human Earth Alliance that suffers infighting and mistrust of one another: the smaller, peaceful and neutral Pacific Ocean island nation called the Orb Union, and the small, technologically advanced Coordinators living on a group of enormous space stations called the PLANTS in high Earth orbit.

Two major events precede the story, known as the Bloody Valentine tragedy that initiated war between the PLANTS and the Earth Alliance when one of the PLANT space station is destroyed by a nuclear bomb, and the counterattack by the PLANTS that buries Neutron Jammers deep into Earth's crust that halts all nuclear reactions and long range radar and radio, causing most areas of earth to go without electricity or communication, and requiring mobile suits to rely on rechargeable batteries.

The story begins in the neutral Orb Union owned space colony Heliopolis, where secret development of advanced mobile suits for the Naturals' war effort is being conducted. The colony is attacked by ZAFT forces, the military of the Coordinators, with the objective of stealing the new units. During the incursion a teenager Coordinator named Kira Yamato, upon seeing his friends in danger, pilots the GAT-X105 Strike mobile suit to fend off the invaders but the colony is critically damaged in the ensuing fight.^[1] As Heliopolis disintegrates, the survivors board an Archangel class assault ship belonging to the Earth Alliance, the Natural's military, and begin their journey to the Alliance base in Alaska.^[2] During the journey to Earth, Kira pilots the Strike to counter a series of attacks by ZAFT but is seemingly killed by his childhood friend, ZAFT soldier Athrun Zala, during one of their battles in which he is nearly killed.^[3] Kira survives the attack and is treated in one of the PLANT space colonies, home to the Coordinators. The Archangel arrives in Alaska but ZAFT launches a full-scale attack on the base overpowering their enemies.^[4]

Kira goes to Alaska with the ZGMF-X10A Freedom, a highly advanced, nuclear powered, and Neutron Jammer proof ZAFT mobile suit stolen by the Coordinator Lacus Clyne daughter of Siegel Clyne, President of the Supreme Council of PLANT. Using Freedom, Kira ends the battle between the two armies, but the base is subsequently destroyed. The Archangel flees to the neutral country of the Orb Union. They subsequently join Lacus Clyne's faction to form the Three Ships Alliance, with the common goal of ending the war between the Naturals and Coordinators. In the midst of the conflict, Athrun learns that Kira survived and searches for him under orders to recover Freedom.^[5] However, after learning of Patrick Zala's, Athrun's father and the radical faction leader of the PLANT Supreme Council, plan to commit genocide Athrun deserts him and joins the Three Ships Alliance.^[6] In a final battle, the Earth Alliance deploys nuclear weapons to destroy the space colonies but are stopped by ZAFT's GENESIS, a super weapon designed to commit genocide on the Naturals. The Three Ship Alliance intervenes to defeat the Earth Alliance's forces and destroy the GENESIS ending the battle. The war ultimately ends as a peace treaty is signed.^[7]