Mysterious immortal humans known as "Ajin" first appeared 17 years ago in Africa. Upon their discovery, they were labeled as a threat to mankind, as they might use their powers for evil and were incapable of being destroyed. Since then, whenever an Ajin is found within society, they are to be arrested and taken into custody immediately.
Studying hard to become a doctor, Kei Nagai is a high schooler who knows very little about Ajin, only having seen them appear in the news every now and then. Students are taught that these creatures are not considered to be human, but Kei doesn't pay much attention in class. As a result, his perilously little grasp on this subject proves to be completely irrelevant when he survives an accident that was supposed to claim his life, signaling his rebirth as an Ajin and the start of his days of torment. However, as he finds himself alone on the run from the entire world, Kei soon realizes that more of his species may be a lot closer than he thinks.
A gun battle takes place in Africa in which a single western soldier outguns many locals, no matter how many times he is killed. He is eventually felled by tranquilizer darts and removed in a U.S. Top Secret body bag. Later, in Japan, Kei Nagai is leaving school, lost in his thoughts, crossing the road, when he is hit and killed by a truck. Within moments, he begins to recover and discovers he is an immortal Ajin, the third in Japan. The bystanders and students realize it too and begin to see the opportunity to receive a large reward for his capture. In shock, Kei screams which immobilizes everyone, allowing him to escape. The police and Yu Tosaki of the government Ajin branch converge on the scene. Kei manages to meet up with Kaito, an old trusted friend, and they flee on his motorcycle.
Kaito takes Kei Nagai into the hills on his motorcycle. While stopping for fuel, Kei is recognised by two criminals in a van who have just abducted a schoolgirl. The criminals follow them and when the boys stop by the side of the road, the criminals attack. The leader pins down Kei and chokes him to death to see if he revives. As Kei loses consciousness a mummified figure or "Black Ghost." materialises nearby. Kei comes back to life and screams again, immobilizing everyone. Kaito recovers first and they flee again on the motorcycle, pursued shortly thereafter by the criminals, who are in turn followed by the Black Ghost. Meanwhile Yu Tosaki orders tranqilizer guns for the police as the best way to stop Ajin. Kaito and Kei manage to cross a railway line, but as the criminals cross the tracks behind them, the Black Ghost immobilizes the driver, and their van is destroyed by an oncoming train. The Black Ghost is heard repeating Kei’s words.
Kaito and Kei are seen and pursued by another motorcyclist. Meanwhile Yu Tosaki recognises Sato, an Ajin hunter at the original accident scene. The other motorcyclist causes the boys to crash, but Kaito recovers and knocks him unconscious. Unfortunately Kei has a broken leg and cannot move. He uses the motorcyclist’s knife to kill himself, and then fully recovers without injuries. Sato and Koji Tanaka discuss ways to find Kei Nagai. Kaito takes Kei to his retreat in the forest where he suggests that they to go to Kyushu Kei sees the Black Ghost again. Yu Tosaki’s assistant, Izumi Shimomura, questions Kei’s sister Eriko who tells her of the time Kei saw a Black Ghost when their dog died. Suddenly a Black Ghost appears and kills Izumi Shimomura and the police officers before her eyes.
Izumi Shimomura recovers and is revealed to be an Ajin. She uses her own Black Ghost to attack the one sent by Koji Tanaka that killed her. The Black Ghosts battle each other, with the one controlled by Izumi Shimomura eventually defeating the one controlled by Koji Tanaka. However Sato abducts Eriko during the battle and tells her that he wants to help Kei. Kei decides that he should try to contact other Ajin who may be in hiding, but Sato contacts him first and they agree to meet. Kei leaves while Kaito is sleeping and meets Sato, but before Kei can decide whether to trust Sato, he is shot by a tranquilizer dart. Sato decides that Kei inexperienced and must be 'educated'.
Yu Tosaki and the police arrive and take Kei into custody. Sato reveals that it was his plot to have Kei captured by the government so that they would mistreat him and thus turn him against humans. The government surgeons begin experimenting on Kei in a sealed room. Under intense pain, his Black Ghost appears, but Kei resists using it to kill the surgeon. Sato and Tanaka mercilessly attack the installation, until Sato finally reaches Kei to free him. However Sato discovers that Kei has not become the vengeful Ajin that he expected, and considers his strategy a failure.
Sato suspects that something is different about Kei and when Sato starts to kill helpless surgeons, Kei objects and kills Sato. In the Ajin research centre, Ikuya Ogura tries to explain the Black Ghosts and Yu Tosaki insists that Izumi Shimomura stay by his side to protect him. Sato hunts Kei to kill him permanently, but Kei decides to help the surgeons escape and act as a decoy. He attacks Sato, but fails and as Sato is about to kill Kei, Kei’s Black Ghost appears and kills Sato. As Kei and the remaining surgeon try to escape the installation, Sato again catches them, so Kei calls his on his Black Ghost but so does Sato. The Black Ghosts attack each other, and neither wins, but the distraction enables Kei to escape to the nearby river.
After losing the 'sample', Kei, Yu Tosaki receives a warning from the minister. He recalls the time when the minister offered him a position in the Ajin Control Commission and where he saw weapons being tested on Ajin 002 for potential profit. As Sato leaves the research complex, he addresses the media and uses them publicize the fact that the government conducts inhumane experiments on Ajin and to announce a public meeting - his strategy being to attract other Ajins to the event. At the event, Tanaka uses his Ajin skills to address only the Black Ghosts of the Ajin present to tell them of the real meeting place. Meanwhile Tosaki pursues his own agenda to get more information about the Ajin. He kidnaps the expert Ikuya Ogura and leaves a damaged body in his place. Later, he visits a hospital where his fiancé lies in a coma because she couldn’t afford the high cost of her treatment.
Kei recovers from drowning in the ocean but then is run into by an old lady on a bicycle. He decides to stop and help her. Sato addresses the seven Ajin who attend his private meeting and gives them the option of joining him in a massacre. Those that don't, he plans to keep as captives. Three decide to join him, but four do not. Two are shot and two run, but only one young boy, Ko Nakano, escapes. Kei helps the old lady home, and although she realises he's an Ajin, takes no action. Kei uses the opportunity to carry out some tests of his own to summon the Black Ghost. Nakano arrives home to find armed men sent by Tosaki to capture him. Before he's caught, an ambulance called by a neighbour arrives and takes Nakano to hospital. He dies, but re-awakens and escapes. Meanwhile Sato records a public message threatening to change public opinion by force, commencing with an attack on a pharmaceuticals company in 10 days.
Ko Nakano comes across Black Ghost tracks and finds Kei Nagai who is now acting as the grandson of the old lady in the village with her consent. Ko suggests that they join forces to fight Sato. Although Kei agrees with Ko, he really wants a peaceful life, and traps Ko in an abandoned truck to restrain him. Meanwhile Sato and the new Ajin prepare for the beginning of the war on humanity. Back at the Ajin Control Commission, Sokabe is assigned to monitor Tosaki, and possibly become his successor. Regardless, Tosaki continues to brutally question his captive Ogura for information about Ajin. After being allowed to smoke his preferred brand of cigarettes, Ogura is prepared to talk.
Ogura starts telling what he knows about Ajin and Black Ghosts or IBMs (Invisible Black Matter). For example: IBMs have individual characteristics and are unstable; last only about 10 minutes; can be generated only 1-2 times per day; are difficult to control in the rain. Kei keeps Ko locked up and continues to try to understand how the Black Ghost behaves, for example he found that it does the opposite of what he tells it to do. Kei is seen in the woods by a local who becomes suspicious. To allay the fears of the local officials, Kei appeals personally to them to accept him into the village. Sokabe reports that Tosaki is acting under his own authority and suspects that he has Ogura, but the minister decides to take no action and continue to monitor him. Sato's group prepare for their attack on the Grant Pharmaceuticals company.
Sato's group puts his plan into action with the assistance of the three new Ajin, sabotaging a building dressed as cleaners. Tosaki coordinates the defense of Grant pharmaceuticals whose CEO does not stop production or send staff home. Kei still keeps Ko captive and refuses to stop Sato, enjoying his life playing the grandson of the old lady. Sato implements his plan, collapsing a nearby 50 story building onto Grant Pharmaceuticals, then challenging the elite Metropolitan Police Assault Team to defeat him.
The Metropolitan Police Assault Team use different tactics to continually kill Sato to prevent him from acting against them. Two of Sato's Ajin begin shooting the police, but are themselves targeted by police snipers. However Tanaka uses his Black Ghost to attack the snipers in turn. A break in the action enables Sato to revive and use his Black Ghost to distract the Metropolitan Police Assault Team so he can wipe them out by firing at close range. After killing them all, Sato calmly walks away. Mr Keita, the villager who saw Kei in the woods, sees the ensuing news coverage and recognises a picture of Kei.
Mr Keita reports Kei Nagai to the police to claim a reward. Yu Tosaki orders all available forces to the area to catch Kei. When Kei is confronted by the police, he uses his Black Ghost to delay them allowing him to escape into the woods. He uses Ko Nakano’s phone to throw the police off his trail, but Tosaki realizes it's a ruse and closes in. Kei releases Ko and they try to escape together, but they are intercepted by Tosaki who shoots them with tranqilizer darts. Kei manages to invoke his Black Ghost to attack Tosaki, but Izumi Shimomura invokes hers to intercept it. The Black Ghosts battle each other, and it gives time for Kei and Ko to revive and run. Shimomura's Black Ghost pursues them, but much to Tosaki's and Shimomura's surprise, Kei manages to keep on recreating his. The boys manage to escape and Kei finally decides it's time for them to take out Sato, blaming him for the destruction of his peaceful life. Sato makes another public broadcast, announcing a 'Second Wave' action to assassinate 15 people involved in the conspiracy against Ajin, and if there is no improvement in the treatment of Ajin, a 'Third Wave' where he intends to rule the country.