The year is 2030. The world is rebuilding from World War III. In Neo-Tokyo, plans are being made to hold the next Olympics in the "old city"--where, thirty-eight years before, the first of the bombs fell. There, a band of teenaged delinquents led by Kaneda encounter 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 a man known only as the Colonel and an underground resistance group, bent on stopping to the Colonel's activities.
Among the resistance, Kaneda meets Kay--a girl he alternately maddens and tries to seduce--and Kay's "brother", Ryu. The resistance leaders include Ryu's superior, Nezu--who publically leads the political party that opposes the government--and a powerful religious leader with precognitive gifts--Lady Miyako.
The Colonel has a number of children 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. Another of the children is the mental giant Akira, so powerful that since the war he has been buried beneath the earth's surface, suspended in cryogenic sleep.
The Colonel's staff subjects Tetsuo to painful experiments which awaken tremendous telepathic potential, who is redubbed Number 41. Unfortunately, as Tetsuo's powers appear, a monstrous side of Tetsuo's nature also surfaces. Able to shrug off the most serious injuries, Tetsuo goes on a killing spree. He murders one of Kaneda's friends and even attacks Kaneda.
Unable to tolerate the notion that Akira may be more powerful than he is, Tetsuo sets out to find his rival. The psychic children, who, like Lady Miyako, fear Akira's power and worry about the disaster Tetsuo may unleash. They use their talents to help Kay and Kaneda follow Tetsuo to the Olympic site, below which Akira rests. There, they are almost reunited with Ryu, who is working undercover as a soldier.
Hoping to prevent a disaster, the Colonel follows with his troops and scientists. Tetsuo easily repels soldiers armed with the most sophisticated weaponry. The scientists monitoring Akira's cryogenic sleep surmise that even in hibernation, Akira's power is responding to Tetsuo's psychic energy.
Kay and Kaneda watch from hiding as Tetsuo reaches Akira's resting place. The cryogenic chamber begins to crack from within, as Akira emerges.
The paranormal giant is still dazed and weak with the aftereffects of his coma. Akira is unable to speak, shy of bright lights, and easily ordered about. Tetsuo and he begin to make their way to the surface, followed by Kay and Kaneda.
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, who are separated by the blasts. Akira is saved by Kay and Kaneda, 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 successfully manages to conceal the truth about what has occurred despite leaks to the media, but he is discredited and made a scapegoat following the disaster. He decides to use the emergency as an excuse to hunt down and destroy the resistance once and for all.
Lady Miyako correctly divines that Nezu can no longer be trusted. She calls upon Sakaki, a young girl trained in techniques of infiltration, observation, and combat, and asks her to find Akira.
Kay and Kaneda take shelter with Chiyoko, a formidable woman in the resistance. Ryu, unaware of what has occurred, reports to Nezu, who scornfully, denies all knowledge of Kay--with whom he has been in contact. Nezu says nothing of Akira, planning to exploit the still-somnolent child for his own purposes. Kay brings Akira to Nezu, who and orders his staff to kill Kay, Kaneda, and Chiyoko. The three manage to escape and head for Nezu's home, where Akira is hidden.
Nezu is caught breaking curfew by soldiers who open fire upon his car. Secretly followed by Ryu, Nezu and his chauffeur evade the army and survive the attack of a caretaker robot. By the time Nezu arrives home, the government has been overthrown by the Colonel's inner circle, and a provisional military regime is in place.
Kay, Kaneda, and Chiyoko manage to free Akira, only to have him stolen from them again. This time it is Sakaki, who almost succeeded in an earlier, similar attempt. Now, she is aided by two other girls, Miki and Mozu. The Colonel, who is frantically trying to find Akira before he fully awakens, arrives on the scene with his three psychic wards. The three warn their master that Sakaki and her allies are also psychically gifted, although not as strongly as themselves.
Mayhem erupts, and Kay, Kaneda, and Chiyoko commandeer a tank and enter the thick of it. Nezu corners Sakaki and Akira, but before he can harm them, Miki sacrifices her life to enable the pair to escape. Enraged, Nezu orders his soldiers to bring Sakaki and Akira back, dead or alive.
If you listen you can hear it. Stop. Stand still. Listen. It is the sound of the city of Neo-Tokyo. It is not a living being but somehow it knows. It hears the gunfire, the cries of the wounded, the tattoo of running, scurrying feet. It knows that something is going to happen. So, the city holds its breath and waits. It remembers Akira. It knows.