The Earth Sphere Federation's autonomous peacekeeping force "A-LAWS", has been suppressing an opposition force called "Cataron", using inhuman tactics and extermination. Saji Crossroad has been working as an engineer on the "Proud" Colony, a space station under construction. When a coworker is discovered to belong to Cataron, Saji is arrested under false charges by A-LAWS and pressed into forced labor. Cataron forces mounts a rescue, but A-LAWS mobile suits appear with orders to exterminate the rescuers and all station personnel to cover up its forced labor operation. Setsuna F. Seiei, infiltrates the colony during the battle and rescues Saji. Setsuna then engages the A-LAWS suits in Exia. Still damaged from its battle four years prior, Exia is no match for A-LAWS' new "Ahead" mobile suit. Setsuna is saved at the last moment by the appearance of Tieria in his new Seravee Gundam. Brought back to Celestial Being's new mothership, Ptolemios II, Setsuna is confronted by Saji who now knows Setsuna's identity as a Meister. Once again joining Celestial Being, Setsuna returns to Earth to recruit Lyle Dylandy as the new "Lockon Stratos".

After entrusting Lyle Dylandy with top secret information pertaining to Celestial Being's activities, Setsuna goes to confront Sumeragi Lee Noriega who, consummed by guilt over the countless lives lost during the organization's military interventions four years prior, found refuge in Bill Katagiri and worsened her drinking condition. Meanwhile, Wan Liu Mei leaks information to Ribbons and Saji Crossroad is given access to Celestial Being's archives and learns about the existence of the Throne Gundams. A-LAWS forces mount an attack on Celestial Being's ship, the location of which was among the data acquired by Ribbons, and Tiera is left alone to defend the Ptolemaios. Setsuna, accompanied by Lyle and Sumeragi, heads towards the ship and boards the 00 Gundam, easily dispatching the attacking units and saving the Ptolemaios.

Celestial Being descended to Earth to launch a raid on a Human Reform League-run prison complex, which holds Allelujah and Marina. A-LAWs forces are deployed to back HRL forces in the area to prevent the raid from being successful. Having been given intelligence by Lockon, Kataron guerrillas also assault the prison to rescue their comrades. Though having no experience in mobile suit combat, Lockon manages to display reasonable combat ability. Setsuna secures Allelujah and Marina during the raid. During an encounter between Soma and Allelujah, the latter reveals her true name, Marie Parfacy, before Allelujah boards the Arios.

Marina speaks to Setsuna, Tieria, Ian and Lasse, thanking them for saving her while making a request for them to be bring her back to Azadistan when Tieria refused at first. On the way to Azadistan, the Ptolemaios 2 is attacked by an A-LAWs navy ship in an ambush and has deployed underwater mobile armor 'Trilobyte' to eliminate the ship. Setsuna, Lockon, Tieria and Allelujah have managed to defeat them, bringing the fight to the surface before Soma and The Masked Man intercepted Setsuna and Allelujah with their customized Aheads. Kataron mobile suits arrive just in time to drive back the A-LAWs ship. Marina and Shirin are then reunited. Meanwhile, Billy has been recruited as an A-LAWs MS development chief due to his grudge with Sumeragi.

Setsuna escorts Marina back to Azadistan after the Meisters stop at Kataron's Middle Eastern base. Saji leaves the base as he does not trust the Celestial Being's action. Suddenly, an Earth Federation ship arrives in the area and detains Saji before Sergei decides to release him. An A-LAWs task force arrives with Mr. Bushido, Soma and Barrack leading the squad before automaton droids were deployed to massacre Kataron guerrillas and civilians. Lockon arrives with Tieria and Alelujah to hold back the A-LAWs task force with Lockon gunning down the droids in rage while Soma hesitates to attack him when she sees the droids attack the guerrillas and civilians. Setsuna and Marina arrive in Azadistan, only to face Ali with a mobile suit as he watches the country burning.

After the Meisters land on the damaged Kataron base in the Middle East, they were greeted with accusations and distrust. At this time, Tieria brings Saji back to the Ptolemaios 2 after he spotted him all shaken up in guilt. A-LAWs launches another operation to sortie against the Ptolemaios 2. The Meisters launch to intercept while Sumeragi is out of action after a flashback of a failed operation she led that resulted in her love interest, Emilio's, death. Saji follows Ian to a Ptolemaios 2 turret, while initially hesitating to do so before he fires it at a GN-X III piloted by Louise Harlevy. Allelujah encounters difficulties while facing Soma and Setsuna with Mr. Bushido. As a result, Setsuna goes into trans-am mode with his 00 Gundam.

To break his stalemate against Mr. Bushido, Setsuna takes an extreme risk by activating the 00 Gundam's Trans-am system in order to win. Soma's Ahead and the Arios are shot down and declared MIA as the Ptolemaios 2 is forced to retreat. Stranded and forced to face each other outside their mobile suits, Soma suffers mental attacks from Allelujah's presence and reverts to her Marie personality. Upon finding them, Sergei eventually decides to let them go and the two are rescued by Lockon. Meanwhile, Marina and Katharon learn the Federation intends to reorganize the Middle East and has dissolved all nations including Azadistan.

During his encounter with Regene Regetta, Tieria learns the Innovators' views on VEDA and Aeolia Schenberg while the A-LAWs obtain two new pilots: Patrick Colasour and Innovator Revive Revival. Tieria and Setsuna go undercover to infiltrate a party with A-LAWs and Earth Federation officials, where Tieria meets with Ribbons Almark, who reveals that according to Aeolia's plan, Tieria should have died with the rest of Celestial Being four years ago. Refusing an offer to join the Innovators, Tieria and Setsuna, who has been exposed to Louise as a member of Celestial Being by Billy, escape in their Gundams.

Setsuna and Tieria face off against Ali Al-Saachez’s Arche Gundam, but are sorely outmatched until Allelujah and Lockon arrive and drive off the Arche. Lockon learns the circumstances behind his brother's death and his motivations for fighting for Celestial Being. The A-LAWs attempt to intercept the Ptolemaios II's return to space; the Ptolemaios' success forces Commander Homer Katagiri to accept the help of the Innovators to prevent any more sacrifices. When Kati sends a message to Celestial Being expressing respect for Leesa Kujo's tactics, Sumeragi realizes that Kati is a member of the A-LAWs and recognizes that Sumeragi is Celestial Being's tactical forecaster.

Surviving Katharon guerrillas, including Shirin and Marina, go to negotiate with the Sairu Kingdom, the only country in the Middle East with considerable military power to oppose the A-LAWs. Meanwhile, Sumeragi leads Celestial Being in returning back to their asteroid base, where Setsuna retrieves the 0-Riser. A subsequent test run of the 00 Gundam's twin drive system reveals the potential of the unit. When the A-LAWs' new orbital weapon fires a particle beam on the Sairu Kingdom's capital, Allelujah's Hallelujah personality returns and Marie senses that Sergei is in trouble.

After the Memento Mori is fired at the Sairu Kingdom, Katharon begins planning an attack to destroy the superweapon. Tieria, after witnessing the devastation, decides to tell his comrades about the Innovators. When A-Laws forces led by Kati launch an attack on Celestial Being's asteroid base, everyone within is forced to flee. During the ensuing battle, Ian Vashti is injured, leaving Saji to deliver the 0-Raiser to the 00 Gundam. The combined unit, the 00 Raiser, is able to dispatch the A-Laws attacking, but when Setsuna activates the Trans-Am system, he and everyone in the area are affected by the particles and Saji and Louise shocked to learn they are fighting on opposing sides.

00-Raiser's increased Trans-Am rate enables it to outclass and outmaneuver the Innovators' mobile suits, forcing them to flee in escape pods as their suits are destroyed. In the aftermath of the battle, Ribbons orders Revive Revival and Bring Stabity to capture 00 Gundam; the Innovators question Ribbons' true knowledge of Aeolia's plan and the twin drive system. Saji, Louise, and Setsuna cope with Saji and Louise's positions on opposing sides.

Katharon's offensive against the Memento Mori superweapon goes poorly, with A-Laws' superior units both nullifying the resistance's missile attacks and decimating their obsolete mobile suits.

After the Memento Mori's destruction, the Ptolemaios 2 is forced to descend to Earth. The Innovators arrive and attack the ship and in the ensuing battle, Tieria reveals the Seraphim Gundam hidden in Seravee to decisively defeat Bring Stabity. Separated from his comrades, Setsuna is lured by Ali Al-Saachez into a meeting with Ribbons, who reveals that he was responsible for saving Setsuna's life as the 0 Gundam's pilot and influencing Veda to ensure Setsuna would become the Exia's pilot.

With assistance and supplies from Katharon, the Ptolemaios 2 is able to continue with its repairs in the mountainous region. However, they are unable to proceed with their plan to break through the siege laid by the Federation, without the currently missing Setsuna and the 00 Gundam. Meanwhile, Setsuna, wounded after his fight with Ali Al-Saachez, is forced to get medical help at Katharon's Suille base, where he is reunited and cared for by Marina. The Ptolemaios 2 is forced to defend itself against an overwhelming number of A-Laws mobile suits, but receives an unexpected respite when the fleet suddenly retreats from its successful offensive to deal with a coup d'état led by Hank Hercule at the African orbital elevator. Despite his injuries, Setsuna sets off towards the elevator and is met by Mr. Bushido, who forces Setsuna to fight against him by demonstrating the Masurao's secret ability: Trans-Am.

A-Laws attempts to retake the Africa Tower using assault automatons to kill both the rogue troops and civilian hostages alike, although the Innovators continue to manipulate the information released to the public in order to conceal the A-Laws' brutality. Meanwhile, Setsuna is locked into a heated battle with Mr. Bushido and his Masurao. Their battle is interrupted with the arrival of the Ptolemaios 2 and the remaining Gundam Meisters. After analyzing the unusual redeployment of Federation troops around the elevator, Sumeragi and Kati both realize, to their horror, that they are anticipating that the elevator will collapse soon and that A-Laws is planning on completely destroying the Africa Elevator. A renewed Memento Mori superweapon is then shown preparing to fire at the orbital space elevator.

Despite the best efforts of the 00-Raiser to destroy the second Memento Mori, the beam fired from the badly damaged satellite weapon is still sufficient to severely damage the elevator; pieces of falling structure begin devastating the surface below. The Gundams' efforts to destroy the falling debris are helped by the combined efforts of Marie's GN Archer, Katharon, the Federation army and Kati's forces after a desperate plea for cooperation broadcasted by Sumeragi from the Ptolemaios 2. In the aftermath, Andrei Smirnov unexpectedly slays Hank Hercule, and soon associates his father Sergei with the coup d'etat. Wishing to avenge his mother's death, Andrei destroys Sergei's unit as Marie arrives too late to intervene.

Four months after the destruction of the orbital elevator in Africa, the world is a different place. The AEU's orbital elevator is rebuilt; Katharon has lost most of its fighting strength and its members are systematically hunted down; the Federation grants A-Laws complete control over the entire military. Despite their success in destroying the second Memento Mori, Celestial Being endures wave after wave of A-Laws attacks, thanks to an oblivious Anew Returner's networking with the Innovators. Tieria suggests to the Ptolemy crew that the time is right for them to carry out a mission to take back Veda. For that purpose, Sumeragi designs a plan centered around capturing an Innovator and the plan begins as A-Laws attacks yet again. Meanwhile, Regene gives Wang Liu Mei the coordinates to Veda's core.

In the course of the Ptolemaios II encounter with an A-Laws task force, Revive is captured after his encounter with Tieria. Saji and Louise meet in battle, the two being transported to an alternate reality and Louise is left shaken in her resolve to fight against him. While Sumeragi and the Meisters interrogate Revive, his presence on the ship causes Anew to reveal her allegiance to the Innovators and declares the hijacking of the Ptolemaios II as she fires her gun at Lasse Aeon. Wang Liu Mei and Hong Long try to leave Ribbon's hideout to deliver Veda's location to Celestial Being, only for their ship to be shot down by Nena Trinity with Gundam Throne Drei.

Anew reveals her allegiance to the Innovators and with Revive attempts to steal 0 Raiser for Ribbons but the machine is retaken, though the Innovators escape. Later they return, with new Suits (including Louise in her Regnant). Lyle attempts to get through to Anew but before he could, he is caught off guard, as Ribbons taken control of Anew. But as she was about to strike him down, her suit is shot by 00 Raiser as the Trans-Am particles have them share one tender moment together before her suit explodes.

Setsuna and Saji head out to Lagrange 5 to locate Wang Liu Mei, who has, along with Hong Long, miraculously survived the attack by the Throne Drei. Nena intercepts the pair and shoots Hong Long, who sacrifices himself to allow Wang Liu Mei to escape. Liu Mei encounters Setsuna, and after giving him the coordinates to Veda, is killed by Nena as she tries to escape.

The duel between Setsuna and Graham ends with Setsuna emerging victorious. However, he chooses not to finish Graham off and leaves. Setsuna and the others soon review Wang Liu Mei's information and determine that a fierce battle against A-Laws will ensue as they journey to Veda's core at L2.

After dealing with Regene Regetta's treachery by having Ali-Al Saachez shoot him, Ribbons Almark reveals his massive colony ship, which he claims is the place where Aeolia Schenberg created Veda, the original GN Drives, and the Innovators. The colony fires a massive particle cannon and destroys most of A-Laws fighting combatants. Celestial Being launches an assault on the Innovator's colony ship and are countered by an army of Bring Stabity and Devine Nova clones, all piloting Trans-Am equipped kamikaze units. In the ensuing battle, Patrick Colasour sacrifices himself to defend Kati's ship and the Seravee is completely disabled by Healing Care and Revive Revival in their newly Trans-Am equipped suits. In the meantime, Setsuna and Saji confront Louise and Andrei; after disabling Andrei's Ahead, Setsuna moves in on the Regnant and Saji contacts Louise. The Ptolemaios II manages to enter the colony under cover from the Arios and GN Archer, but the ship is quickly infiltrated by hordes of automatons. Lockon fights a losing battle against Ali-Al Saachez in his rebuilt Arche Gundam, while Soma's GN Archer runs out of particles and is hit by an Innovator kamikaze. Sumeragi takes a gun and heads out to face the automatons swarming the Ptolemy, but is shocked to find they were accompanied by Billy Katagiri, the supplier of the Innovators' Trans-Am systems, who then pulls a gun on Sumeragi. Inside Veda's core, Ribbons is shocked that Tieria managed to survive Seravee's near-destruction and is now facing him, to which Tieria then pulls a gun on Ribbons.

The battle between the 00 Raiser and the Regnant comes to its conclusion with a Gaga suicide attack. Setsuna and Saji survive the onslaught and manage to pull Louise out the wreckage of her unit before enemy reinforcements arrive. Meanwhile, inside Veda's core, Tieria corners Ribbons Almark but is gunned down. Elsewhere, Louise finds herself in the company of Saji on the Ptolemy and attacks him, only to suffer a nervous breakdown. As the battle escalates with Healing Care and Revive Revival, Setsuna resorts to the 00 Raiser's Trans-Am system, which triggers his abilities as a pure Innovator. As he intercepts the thoughts of his friends, comrades and enemies, he soon realizes the situation is grim. Growing frustrated, Setsuna inadvertently activates the 00 Raiser's Trans-Am Burst system and blankets the battlefield in purer GN particles, causing a momentary halt to the combat. Seizing the moment, Setsuna infiltrates the colony and closes in on Tieria and Veda's position. Meanwhile, Ribbons finds his link with Veda severed by the integrated consciousness' of Regene Regetta and Tieria Erde into Veda's systems. Tieria remotely activates the Seraphim Gundam's Trial System to shutdown all the units linked to Veda within its Trial Field, including the Gagas, Arche, Gadessa and Garrazo. With Veda secured, the forces of Celestial Being wrap up their battles, including Lockon, who finally avenges his family by killing Ali Al-Saachez. Setsuna locates Veda's core and finds Tieria dead but no sign of Ribbons. Before he can pursue Ribbons, Tieria reveals his presence inside Veda to Setsuna and his new understanding of Aeolia Schenberg's plan. Setsuna departs for the Ptolemy but when Ribbons shoots down the Seraphim Gundam in his giant mobile suit, the Reborns Gundam, Setsuna prepares to do battle one final time in the 00 Raiser.

In the final confrontation between Setsuna and Ribbons, the 00 Raiser is heavily damaged by Ribbons and the other Innovators; however, assistance from the other Meisters even the odds. In the ensuing chaos, Allehujah and Hallelujah work together to defeat Hilling Care, while Lockon narrowly manages to kill Revive Revival. Eventually, Ribbons and Setsuna damage each other to the point where neither one can continue fighting. However, Ribbons manages to steal one of the 00's GN Drives, which was 0 Gundam's, and places it in the abandoned 0 Gundam. Setsuna, in turn, takes the remaining GN Drive and installs it back into the Exia. After another difficult duel, Ribbons and Setsuna run through each other with their swords but Setsuna emerges the victor. In the epilogue, the Federation undergoes reforms as its new president disbands A-Laws and pushes for better global peace; Saji and Louise rekindle their relationship; Allelujah and Marie have left Celestial Being to search for the meaning of their existence; Andrei Smirnov stays in the military to preserve peace like his father and mother; Patrick Colasour and Brigidier-General Kati Mannequin marry; Klaus and Shirin work as politicians in the Federation Assembly; Marina returns with the children to lead a rebuilt Azadistan; Graham Aker is seen visiting Billy Katagiri in his office; Lockon and Setsuna leave with Celestial Being (who are still considered dangerous due to their refusal to disband) to space and Tieria disappears into Veda to watch over the world.