The series is set in 2307 AD. As a result of the depletion of fossil fuels, humanity had to search for a new source of power. The power was found in the form of massive arrays of solar power collectors orbiting the Earth, and supported by three orbital elevators, each one serving one of the three "power blocs" on the planet.

With this nearly inexhaustible source of energy benefiting only the major powers and their allies, constant warfare erupts around the globe among minor countries for fuels and energy. Countries that once economically relied on the sale of fossil fuels have plunged into poverty. Some even believe that solar energy threatened the "promised land of God", resulting in the 20-year Solar Wars. This chaos led to the formation of a private military organization, called Celestial Being ,Soresutaru Biiingu?), dedicated to eradicating war and uniting humanity through the use of four humanoid machines called Gundams. Mobile Suit Gundam 00 follows four mobile suit pilots termed Gundam Meisters , sided with Celestial Being. The main protagonist is 16-year old Setsuna F Seiei a quiet, taciturn young man who grew up in the war-torn Krugis Republic. He pilots the GN-001 Gundam Exia, a high mobility mobile suit effective in melee combat.

Unable to counter Celestial Being's superior technology, the three major powers eventually unite into the United Nations Army in order to counter Celestial Being's armed interventions. In order to fight the Gundams, the United Nations Army employed the help of Laguna Harvey. Harvey, a Celestial Being intelligence agent turned traitor, provides them with 30 GN-X, mobile suits equipped with pseudo-GN Drives that are almost on-par with the Gundams. As the United Nations resist Celestial Being's interventions, a second team of Gundams, known as Team Trinity, appears and assists in the Meisters' eradication of war, albeit in a much more cruel and cold-blooded fashion, in contrast with the original Meisters' less-aggressive nature of armed intervention.

Alejandro Corner, a former Celestial Being observer who plans to make use of the chaos and destruction created by Celestial Being to rule a reconstructed world, subsequently takes over Veda, Celestial Being's supercomputer which is located on the moon. Without the tactical aid from the organization's artificial intelligence, Celestial Being is easily overwhelmed and overpowered by the almost as powerful GN-X units and their superior numbers.

The United Nations Army initiates Operation Fallen Angels to destroy the Gundams, having discovered the location of the Meisters' mothership, Ptolemaios. During the operation, Ali Al-Saachez kills Lockon Stratos after a climatic battle. Alejandro Corner, in his unique custom mobile armor Alvatore, attacks Gundam Exia as the GN-X units proceed to destroy the Ptolemaios and the remaining Gundams. Exia struggles with the monstrous Alvatore, but in the end succeeds in killing Alejandro. Graham Aker, an ace pilot of the United Nations Army, then challenges Setsuna to a fight, seeking revenge for his fallen comrades and questioning the purpose of Gundams' existence. The fight results in the destruction of the GN-Flag, while the Exia is heavily damaged.

Saji Crossroad has followed the path to becoming a space engineer, to keep his promise to Louise Halevy. But he ends up being mistaken for a member of the dissident organization, Katharon, and unjustly imprisoned. Louise herself is compelled to become involved in Federation government reform and joined A-Laws as a mobile suit pilot during the four-year gap, using her family inheritance to fund A-Laws research.

Meanwhile, Setsuna, having survived the battle with Graham Aker four years ago, has witnessed a change in the world due to the actions of Celestial Being. Setsuna tries to confront the A-Laws by himself with his battered Gundam Exia, but is easily overpowered by their newer models. He is rescued by Tieria Erde, piloting his new mobile suit, the Seravee Gundam.

By combining the GN-Drives of Exia and 0 Gundam, Celestial Being's engineers manage to complete Aeolia's plan for a mobile suit with a twin drive, the 00 Gundam, which is entrusted to Setsuna. To pilot the two remaining new units, Lockon Stratos' twin brother is invited to assume his brother's former position and pilot the Cherudim Gundam, and after Allelujah Haptism is rescued from the prison he was being detained in during the timeskip, he assumes the command of Arios Gundam.

Oblivious to Celestial Being and the A-Laws, a third party is manipulating both sides of the conflict. This group call themselves "Innovators", composed of Alejandro Corner's former assistant Ribbons Almark, and his six subordinates. Subsequently, it's revealed that Aeolia Schenberg's plan has three phases; unite the world's factions through Celestial Being's armed interventions, unite the will of the world through the A-Laws, and then advance humanity into deep space and undergo Innovation, a trans-human process.