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 sets out in search of Akira, whose powers he fears may rival his own.
Even in hibernation, Akira's power responds to Tetsuo's psychic energy. When Tetsuo reaches Akira's resting place, the cryogenic chamber begins to crack from within and Akira--dazed and docile following his long sleep--emerges.
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. The two 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 uses the emergency as an excuse to hunt down and destroy his enemies. With the aid of his inner circle, the Colonel stages a successful coup d'etat.
Nezu, planning to exploit Akira for his own purposes, kidnaps the child and orders his staff to kill Kaneda, Kay, and Chiyoko, who manage to escape and free Akira. He is, however, stolen from them again, this time by young psychics headed by Sakaki trained by Lady Miyako, who now knows that Nezu has betrayed her. The Colonel, with his troops and his psychic children, is also frantically trying to find Akira before he fully awakens. Sakaki hides Akira in a dumpster. There he is found by Ryu--one of the few people who doesn't recognize the child. Ryu and Akira encounter Nezu, who blurts out the boy's name. Ryu realizes that his former master is a traitor. When Nezu tries to kill them, Ryu guns him down and leaves him for dead.
Ultimately, Sakaki, Ryu, Akira, Kaneda, Kay, and Chiyoko are surrounded by the Colonel's troops. 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 light blast powerful enough to devastate the entire city. Acting quickly, Masaru and Kiyoko sweep most of the people in the area upward, into the shelter of a skyscraper. 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.
Afterwards, as Akira sits alone, telekinetically playing with bits of rubble, Tetsuo finally reappears. 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. 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. In addition, Tetsuo conducts deadly tests on special followers, hoping to find more psychics fit for training. The Empire is even eventually infiltrated by teams of spies sent from the outside to learn the truth about what is happening in the city.
Masaru and Kiyoko are sick with withdrawal from the drug which augments and channels their psychic powers, and Kiyoko tells Kay to find Number 19. They meet with Lady Miyako, who gives them medicine to help Kiyoko and Masaru, and asks that Kay bring the other psychics to her when they are well.
Most of the spies from the outside are hunted down by a clairvoyant, and killed by other chemically created psychics. Only their leader, Lt. Yamada, kills one of the monsters and escapes. Tetsuo's followers are on the verge of catching him again, when Ryu--who has been depressed and drinking heavily following the recent deaths of many of his friends in the resistance--appears and leads him into the safety of an underground shelter.
Meanwhile, Tetsuo's aide picks three pretty girls out of the Empire's breadline for what he thinks will be a fatal orgy. Tetsuo orders them to swallow diluted, recreational strength capsules of the mind-altering drugs. As the orgy begins, so does an odyssey into Tetsuo's mind, and he relives his past, recalling moments of his friendship with the cocky, maddening Kaneda.
Heartbeats race in Neo-Tokyo this day, staccato rhythms that shape the lives of the city. It's a rhythm of unease, when Ryu attempts an alliance with a mysterious figure who may or may not be an American spy. It's a rhythm of madness, with a malevolent forces surrounding Akira eager to extend his empire. And it's a rhythm of hope, as Chiyoko and Kay fight to make their way to the safe refuge of Lady Miyako, the lives of the children Masaru and Kiyoko hanging in the balance...