Twenty-thirty. The world hovers on the brink of World War IV. In a section of Neo-Tokyo known as the "old city"--where, thirty-eight years before, the destruction of World War III began--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. Members of the resistance include Kay, Ryu, and a formidable woman named Chiyoko. Among their superiors is the blind Lady Miyako--a powerful religious leader with precognitive gifts.
The Colonel has a number of children under his control. Each child is identified by a number marked on the hand. At one time Lady Miyako was Number 19. 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. Tetsuo is able to shrug off the most serious injuries. He goes on a killing spree, even attacking Kaneda. Followed by Kay and Kaneda, Tetsuo seeks out Akira, whose powers he fears may rival his own. In hibernation, Akira's power responds to Tetsuo's psychic energy. When Tetsuo reaches Akira's resting place, the cryogenic chamber cracks from within. Akira emerges, dazed and docile following his long sleep.
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 the laser strikes Tetsuo's left arm. Neo-Tokyo is placed in a state of military emergency, with "caretaker robots" patrolling the streets and keeping order.
Akira and the resistance fighters are cornered by the Colonel's troops, but all seems well when Takashi fondly greets Akira. Then, Nezu, a former resistance leader who has betrayed his own side, arrives. He tries to kill Akira, but kills 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. Masaru and Kiyoko sweep most of the people in the area upward. Kaneda is last seen vanishing toward the sky. Afterwards, 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 outside world. 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, finding more psychics fit for training. The Empire is eventually infiltrated by teams of spies sent from the outside world.
The Colonel is alone, living in hiding. The remnants of his forces have joined the survivors of the resistance. Masaru and Kiyoko are sick with withdrawal from the drug which augments and channels mental powers, and when Kiyoko, whose powers are precognitive, tells Kay to find Number 19, Lady Miyako asks that Kay bring the other psychics to her when they are well.
Tetsuo's new psychics kill most of the spies from the outside, but their leader, Lt. Yamada, escapes when Ryu leads him to the safety of an underground shelter. Yamada refuses to tell Ryu who has sent him or let Ryu join him. He does, however, reveal that Russia has conquered part of Japan, and that the Americans' fear of Akira makes the reluctant to get involved.
Tetsuo forces an orgy of sex and drugs on several young girls, only one of whom--Kaori--survives. During it, Tetsuo sees visions of the past, the present and of possible futures. Afterwards, Tetsuo looks into Akira's mind. He emerges a terrified wreck. When he recovers, he decides that Lady Miyako--whose mind he also briefly touched--may be able to explain matters to him. Taking a dose of power-enhancing medication, Tetsuo teleports to the temple of the religious leader. Lady Miyako recounts to him the experiments decades earlier which created the numbered psychics and reveals that the Third World War was begun with a mental blast from Akira. She also warns Tetsuo that he alone can control Akira's near-inconceivable powers, but must first overcome his dependency on drugs. Disgusted and perplexed, Tetsuo departs. On returning to his stronghold, he neglects his duties of state, concentrating instead on trying to kick the habit.
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. The two are brought to safety by the Colonel, who is living in isolation while the last of his scientists attempts to re-establish contact with SOL. Chiyoko, delirious, tells the Colonel to take Kiyoko to the temple, where he'll also find Masaru. Meanwhile, Kay safely conveys Masaru to the temple. There Lady Miyako mysteriously alludes to Kaneda and informs Kay that although Kay herself lacks intrinsic psychic gifts, she serves as a powerful medium for the talents of others.
Ryu and Yamada watch the Empire from hiding. When Tetsuo's dapper assistant--disgusted by Tetsuo's lack of interest in the way Lady Miyako has thwarted their schemes--leads most of the Empire's men out as an army, Ryu and Yamada move in. They are startled by an encounter with Tetsuo, whose withdrawal causes his power to surge erratically. Ryu is even more startled when Tetsuo blurts out what his telepathy has shown him--that the foreign spy has come to assassinate Akira.
Tetsuo's lieutenant leads his army to Lady Miyako's temple, and they slaughters all in their path--monks, penitents and helpless refugees alike. They are, however, thwarted by the power of Lady Miyako's psychically gifted monks and defeated when Kay captures their leader. Lady Miyako refuses to permit the execution of her enemies. Tetsuo's men depart alive, bitterly swearing revenge. They return an hour later hungry for blood and victory. Kay, along with Kai--one of the surviving members of Kaneda's old gang--urges Lady Miyako to flee before it's too late. When the religious leader refuses, they decide to make a last stand with Masaru in the temple's tower--but before they can get the boy to safety, the attack begins.
Power. Its touch, its taste, its feel--that is the order of the day in Neo-Tokyo. It is from the desire for power that Tetsuo's aide once more advances his army into the temple of Lady Miyako, eager for the secrets within. It is in the use of power that the Colonel unleashes his secret weapon--with devastating results. And it is for the meaning of power that Tetsuo is catapulted into a search for an understanding of his psychic abilities, a journey that takes him from the infinity of the stars to the deep recesses of his own soul...