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. In the old city, a band of teenaged delinquents led by Kaneda encounter Number 26--a terrified child possessing extraordinary telekinetic abilities. During the encounter, the paranormal boy gravely injures Tetsuo, one of Kaneda's close friends, then mysteriously vanishes.
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--Kay's "brother", Ryu, and Ryu's closest subordinate, a man who proves his value to the group when he detects and very nearly kills a spy from the Colonel's organization. Ryu's superiors in the resistance include Nezu--who publically leads the political party that opposes the government--and a powerful religious leader with precognitive gifts--Lady Miyako.
The Colonel already has a number of children under his control, each one possessing a distinct set of psychic talents and identified by a number marked on their hand. (Lady Miyako was, at one time, Number 19 in the series.) One of the children the Colonel "controls" is the mental giant Akira. Because of his immense psychic abilities, he has been suspended in cryogenic sleep beneath the half-finished Olympic Stadium for almost four decades.
The Colonel's chief medical advisor, called Doctor, subjects Tetsuo to painful electronic and chemical experiments, awakening tremendous telepathic potential in the boy, who is dubbed Number 41. Unfortunately, as his powers grow, a monstrous side of Tetsuo's nature also appears. Able to shrug off the most serious injuries, Tetsuo goes on a killing spree, eventually murdering one of Kaneda's closest friends and attacking Kaneda, who, along with Kay, is subsequently captured by the Colonel and taken to his installation.
Tetsuo learns of Akira's existence and is unable to tolerate the idea that Akira may be more powerful than he is, so he forces the Doctor to tell him where his rival lies. Determined to seek him out, Tetsuo brutally attacks the Colonel, who tries to restrain him. The psychic children, who, like Lady Miyako fear Akira's power and are worried about the disaster Tetsuo may unleash, and use their talents to help Kaneda and Kay escape from their cells. Armed with a laser, Kaneda routs Tetsuo, who flees the installation and sets out for the Olympic site where Akira sleeps. Before the Colonel recovers, Kaneda and Kay are able to escape "aided" by the same spy Ryu's lieutenant previously left for dead. Although they don't trust the man, Kaneda and Kay bring him along as they, too, head for the Olympic site. Ryu and his lieutenant are working undercover at the Olympic Stadium, posing as soldiers.
Hoping to prevent a disaster, the Colonel alerts his troops and scientists. When everyone finally reaches the site, fighting breaks out.
Tetsuo easily repels wave after wave of soldiers armed with the most sophisticated weaponry. The scientists monitoring Akira's cryogenic induced sleep are appalled to discover that the temperature in Akira's chamber is beginning to rise, and they deduce that even in hibernation, Akira's power is responding to Tetsuo's psychic energy.
Kaneda, Kay and the spy steal one of the army's flying platforms, but are unable to control it. The result is while trying to reach Akira'a chamber, the unlikely trio fly by an elevator platform carrying Tetsuo, Ryu and his lieutenant. The runaway platform, also, rockets by the Colonel, and dozens of hostile troops. The trio barely manages to leap off the platform before it crashes. Now grounded, Kay forces the spy to go his own way. Kay and Kaneda stumble across a map to Number 28's chamber--Akira's chamber. From hiding they watch dumbfounded as Tetsuo strides past them right for the chamber. Meanwhile, the spy corners Ryu's lieutenant on an elevator platform and they begin a fight to the death.
Intense cold from the growing cracks in Akira's chamber begins to spill throughout the site. The Colonel orders his troops to fall back, and take cover. While the scientists are frantic they know it could only mean that Akira is close to consciousness. Just as Tetsuo reaches Akira's resting place, the cryogenic chamber cracks from within--Akira emerges.
The paranormal giant is still dazed and weak with the aftereffects of his sleep, unable to speak, shy of bright lights; Akira is easily ordered about. Tetsuo and he begin to make their way to the surface. Realizing that it is move or perish, Kay and Kaneda also manage to find a way to the surface.
Less fortunate are Ryu's friend and the spy, the Doctor, and a number of soldiers, all killed by the deadly cold. Ryu, ironically, is saved by other soldiers who still believe he is one of them.
Terror sweeps the control room, as the Colonel tries desperately to prevent panicking, but it is too late, a scientist triggers the Code 7 Emergency Alarm. Throughout Neo-Tokyo the civilian defense claxon sounds. Citizens pour into the fallout shelters, lawlessness reigns on the streets, as Neo-Tokyo holds its collective breath waiting for the bombs to fall again. Horrified of what has been unleashed and determined to act before a greater catastrophe occurs, the Colonel summons the powerful SOL military satellite. He orders that its laser cannon be fired at Tetsuo and Akira. The two boys are separated by the blasts. Akira is saved by Kay and Kaneda, but Tetsuo is less fortunate. The laser strikes his left arm.
Through Neo-Tokyo a web has been woven. The web is not silken gossamer, it is hard and cold-forged with a hundred lies, hardened with a thousand treacheries. One man, the Colonel, may have started it, but countless more have helped him weave it until it now reaches everywhere. One single tug from a child called Akira has started unravelling the web. Frantically, the weavers try to remake the strands to perpetuate their treachery--but to no avail. The old web is being swept away, a new web has been started. Akira has risen.