Twenty-thirty. The world stands poised at the edge of World War IV. An explosion of thermo-nuclear proportions has been set off in Neo-Tokyo. The world, particularly the superpowers, wonders what has happened. In Neo-Tokyo in a section known as the "old city", 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.
Among the resistance, Kaneda meets Kay--a girl he alternately maddens and tries to seduce--Kay's "brother" Ryu, and a formidable woman named Chiyoko. Other important resistance members include Ryu's superior--the opposition party leader Nezu--and a powerful religious leader with precognitive gifts, Lady Miyako.
The Colonel has a number of children like Number 26 under his control. Each child possesses a distinct set of psychic talents and is identified by a number marked on the hand. At one time Lady Miyako was Number 19 in this series. 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. Able to shrug off the most serious injuries, Tetsuo goes on a killing spree, murdering one of Kaneda's friends and even attacking Kaneda. Then, followed by Kay and Kaneda, Tetsuo seeks out Akira, whose powers he thinks may rival his own.
Akira's power responds to Tetsuo's psychic energy. His cryogenic chamber cracks from within and Akira emerges dazed after his long sleep.
Terrified of what may occur, the Colonel summons the powerful SOL military satellite and orders that its laser cannon be fired at Tetsuo and Akira. Kay and Kaneda save Akira, but Tetsuo is less fortunate. The laser strikes his left arm.
Neo-Tokyo is placed in a state of military emergency following the disaster. "Caretaker robots" patrol the streets, dealing harshly with looters and restoring order. The Colonel stages a successful coup d'etat.
Nezu betrays the resistance, planning to kidnap and exploit Akira, but is thwarthed by a team of young psychics headed trained by Lady Miyako. Nezu orders his men to kill Miyako's psychics and the resistance fighters, and Ryu guns his former master down. Ryu leaves Nezu for dead.
Ultimately, Sakaki--the sole survivor of Lady Miyako's group--is cornered by the Colonel's troops, along with Ryu, Akira, Kaneda, Kay, and Chiyoko. Sakaki is killed trying to escape. All seems well when Takashi fondly greets Akira and reintroduces him to their fellow psychics Kiyoko and Masaru. Then, Nezu, dying and determined for revenge, arrives and tries to kill Akira, killing Takashi instead.
The trauma of Takashi's death galvanizes Akira, who fully awakens and unleashes a light blast powerful enough to devastate the entire city. Acting quickly, Masaru and Kiyoko sweep most of the people in the area upward. Kaneda is last seen vanishing towards the sky. In the wake of the disaster, Lady Miyako opens her temple and offers shelter and comfort to those in need, gathering large groups of followers.
Neo-Tokyo is completely cut off from the rest of the outside world, and in the western part of the city the Great Tokyo Empire is formed--a monarchy with Akira on the throne and Tetsuo as his Prime Minister. The Empire is eventually infiltrated by teams of spies sent from outside to learn what is happening in the city.
The Colonel is alone, living in hiding. Masaru and Kiyoko are sick with withdrawal from the drug which augments and channels psychic powers. Kiyoko tells Kay to find Number 19. The two meet with Lady Miyako, who gives them medicine to help Kiyoko and Masaru, and asks that Kay bring the other psychics to her.
Most of the spies from the outside are hunted down and killed. Only their leader, Lt. Yamada, escapes. Tetsuo's followers are on the verge of catching Yamada again, when Ryu appears and leads him to safety. Ryu attempts to gain Yamada's trust. But the Lieutenant refuses to tell Ryu who has sent him or let Ryu join him. Yamada does, however, reveal that Russia has conquered part of Japan, and that the Americans' fear of Akira makes the reluctant to get involved.
Three young girls are taken out of the Empire's breadline for the pleasure of Tetsuo. He orders all three to swallow diluted, recreational strength capsules of the mind-altering drugs. As the orgy begins, so does an odyssey into Tetsuo's mind. He relives his past, recalling moments of his friendship with the cocky, maddening Kaneda. Tetsuo awakens to discover two of his bedmates dead. Only Kaori--who secretly palmed her medicine--has survived. Tetsuo is convinced that in some way his mental resonance with Akira is responsible for the odd mental voyage. He takes a peek into the mind of his great Emperor--a peek which leaves him a withdrawn, shuddering wreck. When Tetsuo recovers, he decides that Lady Miyako may be able to explain matters to him. Taking a hefty dose of power-enhancing medication, Tetsuo teleports away in search of the religious leader.
Knowing that Tetsuo's followers are closing in, Kay and Chiyoko try to move Masaru and Kiyoko to Lady Miyako's temple. They are attacked before they can do so, and Kiyoko is carried off. Chiyoko is badly wounded, but she gets Kiyoko back just beyond the borders of Akira's empire. Meanwhile Kay, carrying Masaru to safety is harried by a street gang. One of the gang tries to extort goods from her in return for safe passage. Condemning the man as a common thief, Kay aims her gun.
Secrets whisper through Neo-Tokyo's shattered buildings, over and under its broken roadways. Secret alliances between Chiyoko and the Colonel, forged over the life of the child Kiyoko. Secrets passed back and forth between Lady Miyako and Tetsuo about the powers that stream through both of them. And always, the secrets within the unknowable mind of Akira, secrets awesome and terrible.