In a world where minds can be analysed for potential threats of crime and mental instability, Inspector Tsunemori Akane is sent to deal with her first case, along with fellow inspector Ginoza and a group of Enforcers, latent criminals hired by the police to work for them. Akane’s case deals with an insane man who has taken a woman hostage and raped her, holing himself up in a building inhabited by groups of the homeless.

While Kogami is recuperating from Akane’s Paralyzer shot, she begins to worry about whether she is suited to be an Inspector after the fallout from her first case. On her second day on the job, she begins to learn more about the Enforcers she works with.

Ginoza and Akane, along with the Enforcers, are brought in to investigate a death caused by a Drone at a Drone manufacturing plant. When the Psycho-Pass of the entire staff checks out, they question whether it was an accident or possibly murder.

When the CID is brought in to investigate a disappearance of Kimihiko Hayama, they discover that not only has he been killed, but someone has taken over his net avatar, Talisman. The CID tries to track down the fake Talisman in order to find the killer.

The CID’s hunt for Kimihiko Hayama’s killer leads them to another murder with the same modus operandi. Now it’s up to the CID to figure out how to track down the killer’s real identity and get justice for the victims.

After reading Kogami’s personnel file, Akane attempts to learn more about Kogami’s past and why he ended up as an Enforcer. Meanwhile, the CID detectives attempt to figure out who was helping Kanehara commit murders in the Hachioji Drone incident.

After realizing that the recent murders and the Specimen Case are indeed connected, Ginoza takes Kogami off the case and requests Tsunemori to watch over him. Tsunemori discusses Sasayama's murder with Kogami, and he gives her his one piece of evidence: a blurry image of Makishima. Meanwhile, Makishima, in a study with another older man, reveals the circumstances of Rikako Oryo's father's death and discusses the nature of the shortening life expectancy in this "perfect" world. Later, Rikako continues her crimes with the help of Makishima's colleague, Choe Gu-Sung, and abducts another fellow student who is worried about her friend's disappearance.

With his profiling skills, Kogami determines that the girls' school killer isn't the same murderer from the unsolved case years ago; he explains that the recent murders lack "originality" and pointed social commentary of the previous killings. When he and Tsunemori realize the culprit is one of the students, they locate Rikako - who escapes when one of teachers stops Kogami from executing her. As the Enforcers try to locate her secret routes and hiding places, Rikako flees - but not before everyone discovers her latest creation. Makishima calls Rikako to tell her that she's a disappointment and has one of his colleagues dispose her. In the meantime, Kogami picks up a damaged audio file which was deliberately left by Makishima. Due to Rikako's failure, Makishima develops an interest in Kogami.

Kogami, attempting to track down Makishima, takes Tsunemori to visit his former teacher, Jouji Saiga, who agrees to give her a crash course on criminal profiling; however, Ginoza reprimands her harshly which results into an argument. Afterwards, Masaoka explains to her Ginoza's attitude by revealing his past. In the meantime, Makishima discusses humanity and philosophy with Senguji, who in an earlier interview reveals himself to be nearly a full cyborg. He gives him his next target: Shinya Kougami.

Makishima and Senguji set up a hunt by using Tsunemori's friend Yuki as bait to lure Kogami into an abandoned subway station. Upon entering the station, Kogami discovers Yuki and loses contact with Tsunemori; the two must evade Senguji and his canine drones as a curious Makishima observes from above. Ginoza scolds Tsunemori for letting Kogami go on his own but Masaoka chastises him over his treatment of her. Meanwhile, Makishima rigs the hunt to give Kogami a chance to create a working transponder and, as a result, Kogami makes contact with the group outside and they go in after him.

With a drone delivering him a Dominator, Kogami manages to outwit Senguji and kill him, although he also takes some shots in the process. Just then, Yuki is captured by Makishima, with Kogami too weak to follow. As Masaoka tends to Kogami's injuries, Tsunemori goes alone to pursue Makishima. To her shock, she discovers her Dominator is useless against him as his Crime Coefficent levels are too low, with Makishima attributing his murderous intent to his own free will. He gives Tsunemori the opportunity to try killing him with Senguji's shotgun, but she finds herself unable to do it and is forced to helplessly watch Makishima kill Yuki right before her eyes.

Tokyo, 2120. A massive transport drone crashes, and Unit One’s new inspectors Arata Shindo and Kei Mikhail Ignatov head to investigate. Discovering that Hyper Transport Co. accountant Asahi Rick Fellows is missing, Arata performs a Mental Trace to track him, but finds only his waterlogged corpse. Arata and Kei suspect the crash was staged, and pursue the mastermind who tried to silence Rick.

Unit One has begun to grasp the truth behind the incidents following each other like a line of falling dominoes and team up with the SAD to continue their investigation. Arata guards the governor, who is at risk of being targeted again, while Kei organizes a sting using Kisaragi as bait. When he arrives at the appointed meeting place, however, he finds Shizuka Homura waiting for him.