2030. The world hovers on the brink of World War IV. Kaneda, onetime leader of a delinquent gang, is caught up in the aftermath of a power struggle between a Japanese military research organization--led by a man known only as the Colonel--and a resistance group whose members include Kay, Ryu, and a formidable woman named Chiyoko.
The Colonel once controlled a number of psychic children, each identified by a number marked on the hand. Among them were Kiyoko and Masaru--Numbers 25 and 27. The blind Lady Miyako--Number 19 now heads a great religious cult. Number 41 is Tetsuo, who lost his left arm to a laser blast from the Colonel's military satellite SOL, and has used cybernetics and telekinesis to fabricate a prosthetic replacement. Tetsuo was Kaneda's dearest friend until he used his burgeoning powers to slaughter other members of their gang. Now, Kaneda is out for revenge.
Most powerful of all the children is Number 28--Akira--a docile and enigmatic boy who was placed in cryogenic sleep almost forty years ago, after he started the Third World War with a mental blast. He was recently reawakened by Tetsuo, and again he devastated the reconstructed city of Neo-Tokyo. Japan now exists in a state of emergency. The forces of the army and the resistance are scattered, and the military's formidable caretaker robots patrol the streets.
In the western part of Neo-Tokyo, 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, organizing their subjects into fighting units to defend their land. Their headquarters is Neo-Tokyo's Olympic Stadium. To the east, Lady Miyako welcomes refugees to her shrine. In this, she is aided by Kiyoko, Masaru, and a number of loyal, psychic monks.
The Empire is infiltrated by teams of spies and commando units from the outside world, equipped with biochemical armaments which take a tremendous toll on Tetsuo's forces.
A fleet of foreign ships waits in Tokyo Bay, poised for action. Aboard an American naval vessel, an international conclave of scientists and one Tibetan monk study the Akira phenomenon--which they've codenamed Juvenile A. One of the scientists--Stanley Simmons--goes ashore to implement a secret plan. The research team is certain that using military force against Akira and Tetsuo can only lead to disaster.
Meanwhile, Kay joins Miyako's forces in battle against Tetsuo. Kay is a powerful medium, through whom the others can project their powers and strike as one. Kaneda teams up with Kai and Joker-- a rival from his gang days. Using salvaged weapons the trio lead a force of refugees and street rats to help Kay in her battle with Tetsuo. As they fight, Akira looks placidly on.
Then, the international fleet in the harbor sends fighter planes to rain death upon Neo-Tokyo, causing chaos among all the combatants. Enraged, Tetsuo teleports himself to space, seizing control of an orbiting laser cannon. He fires the weapon at the fleet, and then brings it crashing down upon the flagship, killing the commanders and forcing mass evacuation of military personnel and the few scientists who survive.
Griefstricken over the death of his gentle girlfriend Kaori, Tetsuo carries her body to the underground chamber where Akira once slept. Drawn by the similarity of their powers, Akira follows Tetsuo. Along the way, he is joined by Kaneda, Joker, Chiyoko and Ryu. They plan to fight in the bowels of the earth, where many of their comrades died.
Tetsuo's powers have grown erratic. His body frequently bloats and expands, engulfing those who venture too close. For a moment, it seems that contact with Kaneda has restored Tetsuo's humanity. Then, his power comes surging back, and Kaneda is drawn into his monstrous form, apparently consumed. As the battle rages, Akira becomes more alert. Terrified of what might occur if Akira fully awakes, Ryu panics. He draws a gun and shoots Akira, setting the boy's power free.
Seeking a new power source for himself, Tetsuo flies to Lady Miyako's shrine, with Kay in hot pursuit. Lady Miyako instructs Kiyoko and Masaru to look after Akira, and the pair teleport away to help their friend. Lady Miyako, her followers, and Kay prepare to make a final stand against Tetsuo.
Kiyoko and Masaru meet Akira on the psychic plane, and are joined by the spirits of all the gifted children who have died before, hoping to use Akira's power once more.
Telling Kay that the resolution depends on her, Lady Miyako heroically draws Tetsuo's attention to herself and is killed. As she dies, she, too, is drawn to the spirit plane, where the souls of friends who have gone before await. Kay is guided in battle by her late mentor's commands, and is able to break through to Tetsuo. His concentration interrupted, he is vulnerable, and is himself consumed by force from Akira's mind.
Trapped within Tetsuo's soul, Kaneda experiences a fractured, kaleidoscopic journey through his late friend's life and hardships, sharing with Tetsuo both the good memories and the bad.
Kaneda is contacted by Lady Miyako's spirit, and is stunned by what she is told. Although Tetsuo and Akira were created in laboratories, they, and all the catastrophe they bring, are a vital part of mankind's future evolution.
The end is near, for the signs have come to pass; look, and you may see them, too. In a place dancing with stars, a young girl known as Kay commands a machine that spits down fire born in the sun. A triad of children hovers over the city of Neo-Tokyo, weaving strategies of extraordinary forces. The streets below rumble as mental energies collide with the physical, remakinga world. Cut off from her flock, a leader named Lady Miyako screams of salvation and sacrifice. And inside what was once a boy called Tetsuo, things sinister and spiritual battle for control of a human soul.