Twenty-thirty. The world hovers on the brink of World War IV. In a section of Neo-Tokyo known as the "old city"--where, thirty-eight years before, the destruction of World War III began--a band of teenaged delinquents led by Kaneda encountered Number 26--a child named Takashi who uses extraordinary telekinetic abilities to injure Tetsuo, one of Kaneda's close friends.
As a result Kaneda and Tetsuo become entangled in a power struggle between a mysterious military and scientific organization led by the Colonel and an underground resistance group bent on putting a stop to the Colonel's activities. Members of the resistance include Kay, Ryu, and a formidable woman named Chiyoko. Among their superiors is the blind Lady Miyako--a powerful religious leader with precognitive gifts.
The Colonel has a number of psychic children under his control. Takashi, Kiyoko, and Masaru are identified by numbers marked on their hands. Lady Miyako was, at one time, Number 19. Number 28 is Akira, so powerful that since the war he has been suspended in cryogenic sleep.
The Colonel's staff conducts experiments which awaken tremendous telepathic potential in Tetsuo, who is redubbed Number 41. Tetsuo is able to shrug off the most serious injuries. He goes on a killing spree, even attacking Kaneda. Followed by Kay and Kaneda, Tetsuo seeks out Akira, whose powers he fears may rival his own. In hibernation, Akira's power responds to Tetsuo's psychic energy. When Tetsuo reaches Akira's resting place, the cryogenic chamber cracks from within. Akira emerges, dazed and docile following his long sleep.
The Colonel summons the powerful SOL military satellite and orders that its laser cannon be fired at Tetsuo and Akira. The two are separated by the blasts. Akira is saved by Kay and Kaneda, but the laser strikes Tetsuo's left arm. Afterward, Neo-Tokyo is placed in a state of military emergency, with "caretaker robots" patrolling the streets and keeping order.
Akira and the resistance fighters are cornered by the Colonel's troops, but all seems well when Takashi fondly greets Akira. Then, Nezu, a former resistance leader who has betrayed his own side, arrives. He tries to kill Akira, but kills Takashi instead.
The trauma of Takashi's death galvanizes Akira. He fully awakens and unleashes a light blast powerful enough to devastate the entire city. Masaru and Kiyoko sweep most of the people in the area upward. Kaneda is last seen vanishing toward the sky. Afterwards, Lady Miyako opens her temple and offers shelter and comfort to those in need, gathering large groups of followers in the East.
Neo-Tokyo is completely cut off from the outside world. In the western part of the city the Great Tokyo Empire is formed--a monarchy with Akira as the figurehead and Tetsuo as his Prime Minister. Together the pair use their powers, healing the sick, wielding control of the faithful, and organizing their subjects into fighting units that destroy caretaker robots and conquer military and medical relief parties sent from the outside world. The Empire is eventually infiltrated by teams of spies sent from the outside.
Masaru and Kiyoko are sick with withdrawal from the drug which augments and channels mental powers, and when Kiyoko, whose powers are precognitive, tells Kay to find Number 19, Lady Miyako asks that Kay bring the other psychics to her when they are well.
Tetsuo's men kill most of the spies from the outside, but their leader, Lt. Yamada, escapes when Ryu leads him to the safety of an underground shelter. Yamada refuses to tell Ryu who has sent him. He does, however, reveal that Russia has conquered part of Japan, and that the Americans' fear of Akira makes the reluctant to get involved.
Tetsuo forces an orgy of sex and drugs on several young girls, only one of whom--Kaori--survives. Afterwards, Tetsuo looks into Akira's mind. He emerges a terrified wreck. When he recovers, he decides that Lady Miyako may be able to explain matters to him. Taking a dose of power-enhancing medication, Tetsuo teleports to the temple of the religious leader. Lady Miyako warns Tetsuo that he alone can control Akira's near-inconceivable powers, but must first overcome his dependency on drugs. Disgusted and perplexed, Tetsuo returns to his stronghold. There he neglects his duties of state, concentrating instead on trying to kick the habit.
Kay and Chiyoko try to move Masaru and Kiyoko to Lady Miyako's temple, but are attacked by Tetsuo's followers, who escape with Kiyoko. Chiyoko rescues the girl, but is badly wounded. The two are brought to safety by the Colonel, who is living in isolation. Chiyoko, delirious, tells the Colonel to take Kiyoko to the temple, where he'll also find Masaru. Meanwhile, Kay safely conveys Masaru to the temple.
Ryu and Lt. Yamada watch the Empire from hiding. When Tetsuo's dapper assistant--disgusted by Tetsuo's lack of interest in the way Lady Miyako has thwarted their schemes--leads most of the Empire's men out as an army, Ryu and Yamada move in. They are startled by an encounter with Tetsuo, his power surging erratically from withdrawal. Ryu is even more startled when Tetsuo blurts out what his telepathy has shown him--that Yamada has come to assassinate Akira.
Tetsuo's lieutenant leads his army to Lady Miyako's temple, and they slaughter all in their path--monks, penitents and helpless refugees alike. They are, however, thwarted by the power of Lady Miyako's psychically gifted monks and defeated when Kay captures their leader. Lady Miyako refuses to permit the execution of her enemies. Tetsuo's men depart alive, bitterly swearing revenge. They return an hour later hungry for blood and victory.
Kay, along with Kai--one of the surviving members of Kaneda's old gang--urges Lady Miyako to flee before it's too late. The religious leader refuses, so the three board Lady Miyako's private elevator with Masaru and depart for the temple's tower to make a last stand.
The Colonel arrives outside the temple with Kiyoko. He is wounded by some of the Empire's men, but is rescued by a soldier formerly under his command. The Colonel reveals his possession of a remote control laser gun that enables him to fire blasts from the SOL military satellite.
Lady Miyako's elevator reaches the tower. The doors open to reveal Tetsuo, sweating, delirious, and undergoing severe physical trauma from drug withdrawal.
Tetsuo's physical symptoms culminate in an explosive leap skyward that unleashes even further devastation on Neo-Tokyo. During the mayhem, Kanedareappears, as if from nowhere.
Tetsuo hallucinates wildly, experiencing recollections of his parents and his early childhood. He is humbled by a vision of the double helix spiral that Akira constantly creates when he plays. Only Kaori is there to see Tetsuo return to the seat of the Great Tokyo Empire and bow down to his young lord.
The Thieves' Quarter of Neo-Tokyo becomes the backdrop for Kaneda to forge new unions with old friends...and old enemies. The cold light of an early dawn sets the stage for an uneasy alliance between Kay and the Colonel. And the mighty war machines of the superpowers are the setting for a meeting of the world's most brilliant minds, men and women united in a desparate effort to understand the mystery and power of Akira...while a world still remains in which to understand anything at all.