Twenty-thirty. The world stands poised at the edge of World War IV. An explosion of thermonuclear 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, her "brother" Ryu, and a formidable woman named Chiyoko. Other important resistance leaders include Ryu's superior--the opposition 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 seeks out Akira, whose powers he thinks may rival his own. When Tetsuo reaches Akira's resting place, the cryogenic chamber cracks from within and Akira--dazed and docile following his long sleep--emerges.
The Colonel summons the powerful SOL military satellite and orders that its laser cannon be fired at Tetsuo and Akira. 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 following the disaster. "Caretaker robots" patrol the streets, dealing harshly with looters and restoring order.
Nezu betrays the resistance, planning to kidnap and exploit Akira. But he is thwarthed by a team of young psychics and then by Ryu, who guns his former master down. The resistance fighters and Akira are cornered by the Colonel's troops, 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. He acccidentally 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. Acting quickly, Masaru and Kiyoko sweep most of the people in the area upward, and Kaneda is last seen vanishing toward the sky. In the wake of the disaster, 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, 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. The Empire is eventually infiltrated by teams of spies sent from outside to learn what is happening in the city.
The Colonel is alone, living in hiding. Masaru and Kiyoko are sick with withdrawal from the drug which augments and channels mental powers, and Kiyoko tells Kay to find Number 19. The two meet with Lady Miyako. She gives them medicine to help Kiyoko and Masaru, and asks that Kay bring the two psychics to her.
Most of the spies from the outside are hunted down and killed. Only their leader, Lt. Yamada, escapes. When Tetsuo's followers are on the verge of catching Yamada again, Ryu appears and leads him to safety. Ryu attempts to gain Yamada's trust, but the Lieutenant refuses to tell Ryu who has sent him or let Ryu join him. Yamada does, however, reveal that Russia has conquered part of Japan, and that the Americans' fear of Akira makes the reluctant to get involved.
Three young girls are taken from the breadline and given to Tetsuo for his pleasure. He orders the girls to swallow capsules of mind-altering drugs. Only one girl--Kaori--who palmed her capsule survives. Under the influence of the drugs, Tetsuo relives his past. He sees visions of the present and the possible future as well. Afterwards, believing that mental resonance with Akira is responsible for the odd mental voyage, Tetsuo looks into the mind of his Emperor. He emerges a withdrawn, shuddering wreck. Once recovered, Tetsuo decides that Lady Miyako--whose mind he also briefly touched--may be able to explain matters to him. Taking a hefty 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 from human children. She states that the designations in the twenties were reserved for those of the greatest power. Lady Miyako also reveals that the World War III began with a mental blast from Akira which destroyed Tokyo and killed the scientist who created the psychics. Finally, she warns Tetsuo that he alone can control Akira's near-inconceivable powers...but must first give up the drug crutch. Disgusted and perplexed, Tetsuo departs.
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. Chiyoko and Kiyoko are brought to safety by the Colonel, who is living in isolation while the last of his scientists attempts to re-establish contact with the SOL satellite. Chiyoko, delirious, tells the Colonel to take the child to Lady Miyako's temple, where he'll also find Masaru. The Colonel departs in a caretaker robot with Kiyoko. Meanwhile, with the assistance of Lady Miyako's monks, Kay eludes a street gang and 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. They move in 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 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 Yamada has come to assassinate Akira.
Tetsuo's assistant leads his army to Lady Miyako's temple. The army slaughters all in its path--monks, penitents and helpless refugees alike--determined to kill Lady Miyako and capture Kay and Masaru.
Amidst the chaos still rolling through Neo-Tokyo, Lady Miyako's temple was once a refuge, a place of comfort and healing for the troubled injured masses. Once...but no more--now it is a trap, four walls that allow no escape from Tetsuo's aide and the army he's assembled to advance his own power. The army drives forward ruthlessly, intent on seizing Kay and the psychic child, Masaru, crushing back Lady Miyako and her monks--modern weaponry against mental telepathy, the only common ground between the pool of red spreading out around them both...