Twenty-thirty. The world stands poised at the edge of World War IV. An explosion of thermonuclear 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 his own 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, but 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 coherent light blast powerful enough to devastate the entire city. Acting quickly, Masaru and Kiyoko sweep most of the people in the area upward, and 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 in the east.
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, and 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. When Tetsuo's followers are on the verge of catching Yamada again, 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.
Taken from the breadline, three young girls are given to Tetsuo for his pleasure. He orders the girls to swallow capsules of the mind-altering drugs. Only one girl--Kaori--who palmed her capsule survives. Under the influence of the drugs, Tetsuo relives his past, sees visions of the present and the possible future as well. Afterwards, believing that mental resonance with Akira is responsible for the odd mental voyage, Tetsuo looks into the mind of his Emperor. He emerges a withdrawn, shuddering wreck. Once recovered, Tetsuo decides that Lady Miyako--whose mind he also briefly touched--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. Lady Miyako recounts to him the experiments decades earlier which created the numbered psychics from human children. She states that the designations in the twenties were reserved for those of the greatest power. Lady Miyako also reveals that the World War III began with a mental blast from Akira which destroyed Tokyo and killed the scientist who created the twenties group. Finally, she warns Tetsuo that he alone can control Akira's near-inconceivable powers; by giving up the drug crutch. Disgusted and perplexed, Tetsuo departs.
Kay and Chiyoko try to move Masaru and Kiyoko to Lady Miyako's temple. They are attacked by Tetsuo's followers, who escape with Kiyoko. Chiyoko rescues the girl, but is badly wounded. Meanwhile Kay, carrying Masaru to safety is harried by a street gang. Making short of the one who corners her, Kay is met by Lady Miyako's followers and escorted with Masaru to the safety of the temple. Chiyoko is pursued into a rat-infested sewer, when she and Kiyoko are saved by the Colonel. Chiyoko, nearly unconscious, tells her former enemy where to find Masaru. She urges the Colonel to take Kiyoko to Number 19.
Neo-Tokyo is not a war--but one would never know it from the battles that rage in the city. There is the Colonel, fighting for the lives of Chiyoko and Kiyoko. There is Tetsuo, facing off against the foreign warships positioned ominously off the coast. And there is the army of the Emperor Akira, marching on the temple of Lady Miyako, setting brother against brother in a conflict that looses the shattered city's hold on survival...and sends it spiraling down into a dark night of slaughter.