In the underground city of Lux, Ichise is a prizefighter. A man from the ruling Organo syndicate cuts off Ichise's arm and leg as punishment for his treatment of his promoter's girlfriend, who jabbed him in the eye with her finger during sex. The man wants to finish Ichise off, but he is stopped by his boss Keigo Onishi, who doesn't believe in killing a "stray dog". Doc, formerly a citizen of the sealed city of the Class, is Lux's most talented researcher of Texhnolyze, a technology of prosthetic limbs that the user directly controls with the mind. Texhnolyze, whose manufacture and sale is linked to the Organo, uses Raffia, a substance derived from dead bodies that is harvested in mines around the city's Obelisk. Raffia prevents the user's body from rejecting the Texhnolyze. Doc finds a dismembered Ichise near-death in the streets of Lux, and takes him to her lab, where she gives him a new set of Texhnolyzed limbs without his consent.
Ran, a girl who can see the future and is worshiped in the city of Gabe, sells flowers in Lux. Ran is this generation's Seer, which grants her the ability to see "one possibility" of people's futures; each generation, a girl with such abilities is born in Gabe. Her followers unquestioningly accept the fate that she predicts, even if it costs them their lives. Gabe is home to the former leaders of Lux, who were eventually overthrown by the Organo. Onishi, the leader of the Organo, can "hear the voice of the city", and is credited with the current peace in Lux.
Yoshii comes to Lux from the legendary surface. He first arrives in Gabe, where Ran seems to be drawn to him. She takes Yoshii to the Elder, and then has a vision of the Elder dying. Suddenly, an assassin from the Salvation Union tries to kill the Elder, but Yoshii saves him. The Elder lets Yoshii pass into Lux, a city that is distinguished with a massive Obelisk that presumably acts as a power source. It is in Lux where Yoshii becomes immersed in the politics, hierarchy and gangs within the city. Fed up with the unchanging nature of life above, Yoshii is excited about the possibilities a city like Lux has to offer. After being taken in briefly by Shinji and the Racan, Yoshii covertly throws Lux into chaos, pitting the Organo, the Texhnolyze-hating Union, and the marauding and violent Texhnolyzed youths of the Racan against each other, hoping to force the Class to intervene. Ichise escapes from Doc's lab, but is encountered by the men who had originally dismembered him. Ichise tries to fight back with his new limbs, but can't control them well enough, and is thrown in the sewer. Ichise is led out of the sewer by Ran, who seems to be drawn to Ichise for some reason. Ichise gradually gets used to his new limbs, and in another encounter with the man who dismembered him, he kills him with brutal efficiency.
As gang-related retaliations rise, tensions begin to deepen in the city between factions. This culminates in a face-off in the streets of Lux between Onishi and his faction against the Union leader Kimata and his men. Shinji and the Rakan arrive to throw a wrench in the proceedings, and the showdown reaches a breakpoint when Ichise runs into the fray, aiming for Shinji. The three factions suffer casualties, and Shinji gets into a brief sword fight with Onishi, but Onishi and Ichise are extracted by his secretary. Yoshii watches the events transpire from afar, and decides that it's time for the final step. Later, he arrives at the Racan's hangout and takes Shinji to a meeting between the "Great Father" of the Organo and a member of the Class, urging Shinji to "fulfill his purpose" by assassinating the Class emissary, an unspeakable crime in Lux. Shinji refuses, deducing that Yoshii was responsible for the chaos. Onishi arrives to stop the assassination, and Yoshii tries to kill him. However, Ichise saves Onishi in return for saving his life, and kills Yoshii.
After the chaos settles down, members of the Organo begin plotting their next move. Underboss Kohakura tries to advise Onishi to watch his back. Kohakura's assistant Toyama takes Ichise under his wing, and teaches him the ways of the Organo. Over time, they begin to recognize a kindred spirit within each other. Onishi takes Ichise to Gabe and has a sit down with the Elder, where it is revealed that they are amassing a stock of weapons for the Class. Ichise's future is reluctantly seen by Ran, who has been avoiding him since Yoshii's death. Ran tells Ichise that he "will hurt many people, and in the end, [he] will be all alone." Ichise is severely wounded by Ran's words, and refuses to accept them as true.
Doc is fed up with the growing unrest in Lux, and wishes to return to the Class. She visits the elaborate Class enclave known as "the Hill", and tries to convince Kano, a high-ranking member of the Class, to take her in and use her Texhnolyze expertise. She presents Ichise as an example that Texhnolyzation can create perfect humans, but Kano has a different form of Texhnolyzation in mind, so he destroys her research and tries to kill her instead. It is around this time that a mysterious new faction is killing members of all three gangs in the city. Top executives of the Organo begin to grow wary of each other, and try to have each other assassinated. The people of Gabe begin to suffer mysterious casualties, and as their numbers dwindle, the Elder simply accepts this as the Seer's prediction, and therefore "inevitable". Once the most committed organization in Lux, the Union is too split in half, when the second-in-command reveals he has met someone (Kano) with a more highly evolved ideology than Kimata.
Many deserters from the city's three opposing factions willingly or unwillingly join Kano's army of Shapes: humans whose bodies and life functions have been replaced with a Texhnolyzed body, with only the person's head remaining unchanged. Shinji's best friend takes his soldiers and abandons the Racan after a mutual love-interest shows disdain for him. Finally, the Organo becomes dissolved when it is revealed that Kohakura had been orchestrating the internal strife, and only Onishi's faction remains in opposition. Before becoming fully committed to Kohakura and Kano, Toyama has one last drink with Ichise, knowing they will be on opposite sides the next time they meet.
Sensing that Lux is in for the most devastating battle the city has seen, Onishi sends Ichise to find Doc, who has fallen into a drunken depression since she was marked for death by the Class. Kano begins to "speak" to the people of Lux, presumably using the Obelisk to connect with them. He tells the people of Lux to embrace his new form of Texhnolyzation or die. As the Shapes begin to march into the city, Onishi and his faction and Kimata and his remaining soldiers combine forces for the confrontation. Before the fight, Kimata reveals to his wavering followers that the reason he had been so against Texhnolyzation was because he had a procedure done himself, but over time, it had destroyed his body. He allows his followers the opportunity to leave him if they can't accept this. In response, the remaining Union members stand behind their leader.
The battle is a bloodbath and the Shapes have more numbers organized. Onishi briefly encounters Kohakura during the battle, who has been turned into a Shape. As the Shapes begin to overpower the gangs, Kimata tells Onishi that the Opera House is where Kano's stronghold is, so he rushes to get there. Eventually, he is outnumbered and killed by the Shapes. This causes Onishi to order a retreat for both Union and Organo, but the remaining men of the Union rush into the line of fire in response to the valiant death of their leader. Onishi goes underground with the survivors, and eventually reconnects with Ichise and Doc.
In a last ditch effort to stop the end of Lux, Onishi sends Doc and Ichise to warn the surface dwellers of Kano's impending invasion, but they discover that the world above is a deathly silent utopia made up of suburban neighborhoods and office buildings with miles of dirt road in between, with very few people living there. The remaining citizens—the original members of the Class—resigned themselves to extinction and became ghosts. Doc goes to the government office to try and explain Kano's impending invasion, but the entity she speaks to tells her that it doesn't matter what happens. After exploring the nearly empty town, Doc and Ichise wander into an old-style movie theater. Doc and Ichise see a film that explains that Lux was created when the Class rounded up people who were thought to be imperfect or impure of thought, killing many and forcing the rest into the underground city.
Doc commits suicide after seeing what the surface has become. Ichise tries to return home, but is intercepted by a fully Shaped Toyama, who tells Ichise that Ran has been captured by the Shapes and Onishi is most likely dead. They fight briefly, with Ichise killing his "brother". He returns to Lux alone. In Lux, the Shapes have begun to stop functioning, and Shinji uses this opportunity to perform an assault on the Class, the faction that he had always wanted to join. He kills almost everyone in their fortress on the Hill, and even destroys their Raffia supply. However, in the glee of battle, he is shot by Kano's assistant, who then kills himself.
Ran, who knows there's little time left, shows her visions to the people of Lux, driving them mad. She is captured and taken to Kano's sanctum, where he wants her to read his future. The city begins to come apart mentally, including Onishi's surviving men. Onishi stands alone in front of the Obelisk, begging the city for an answer. The city finally speaks to him (with Ran's voice) and asks Onishi to kill it for driving Lux insane. As Onishi listens, several insane citizens creep up behind him with their guns drawn. Onishi chooses to listen to the city, preferring to destroy everything rather than living on with madness in body and soul. He stabs the Obelisk, where Ran went earlier to "connect" with Lux, and it bleeds. Ichise witnesses the crazed men of the city shoot Onishi until nothing is left but his Texhnolyzed legs. Ichise is despondent and can barely contain his emotions. The Lux citizens notice him as "the one that got into the Organo", and go to tear him apart. Ichise remembers Ran's prophecy in Gabe as he murders all of these men.
All of the Shapes, as well as Kano, have been rooted to the ground and permanently immobilized. The remaining members of Gabe took their own lives before the Shapes could reach them, and the Elder threw himself into the Raffia pool after begging Ran for forgiveness. Ichise makes the long walk to the Opera House, where he feels Ran's presence. He runs into an immobilized Kohakura, who laments how he wished he had "advised Onishi better". Ichise takes his battery and continues to the Opera House, where Kano sits immobilized in view of a miniature model of the Obelisk. Kano says that he failed in his attempt to use Texhnolyzation to get people to evolve out of their violent ways, and now humanity's self-preserving bloodline has returned to its roots. Ichise has no interest and keeps asking where Ran is. When Ichise comes closer, he sees what is behind Kano: Ran was turned into a Shape, but Kano says that she turned her mind off by her own will. Ichise can barely contain his rage and he looks like he's ready to pounce. Kano notices this and says that if Ichise kills him, the one sane man in the city, Ichise will only be embracing his own madness. Ichise responds by punching Kano's head off.
As the series ends, Ichise is shown dropping Ran's remains into the pool of Raffia. He leans against a column, watching a projection of a simplistic rendering of one of Ran's flowers. Eventually he slumps over and smiles as he and the city fade away.
