In a distant future, Earth has become a wasteland and humanity as we know it has died out. All that remains are sentient robots. They were supposed to be able to live forever—until the one called Luna died and the Ruin started. Their bodies will rust, and there is nothing that can be done to fix it. Now the robots are left only to contemplate their deaths, kept going only by the rumor that if they eat the one called Casshern, they will gain immortality. Casshern knows nothing about his past, why he exists, or what he is, but he must find out, or he will face the constant torment of being hunted by robots who don't want to die. Casshern leaves death wherever he goes, but he must face it if he is to find out the truth of this world.

In the Japan of the future, employing androids for various purposes is nothing out of the ordinary. However, treating androids on the same level as humans is frowned upon, and there is constant paranoia surrounding the possibility of robots defying humans, their masters. Those who appear too trustworthy of their androids are chided and labeled dori-kei, or android-holics. High school student Rikuo Sakisaka notices when his house droid, Sammy, starts behaving curiously—she has been leaving the house without his instruction. When he inspects the movement logs in her database, a cryptic line grabs his attention: Are you enjoying the time of EVE? Accompanied by his friend Masakazu Masaki, Rikuo tracks the whereabouts of his houseroid to a cafe called Time of Eve, where it is forbidden for customers to display prejudice against one another. The cafe, Rikuo realizes, is frequented by both man and machine, with no evidence to tell either apart. Each customer—from the cheerful Akiko, to a robot dangerously close to breaking down—has their own story and challenges to overcome. While Rikuo tries to reveal Sammy's intentions, he begins to question the legitimacy of the fear that drives humans to regard androids as nothing more than mere tools.

Asuta Jimon, a runaway, is wandering the streets at night when he has a chance encounter with a young girl collapsed beside her tricycle. After he offers her some food, she is moved by his kindness and asks him to join her organization, offering him a face mask and a sweet bun. In need of a place to stay, Asuta decides to play along and accepts her offer, adopting the nickname Dva. Little does Dva know, this cute girl is Kate Hoshimiya, the leader of Zvezda, a secret organization bent on world conquest. However, he soon realizes the true weight of her words as peculiar happenings rope him deeper into Zvezda and its eccentric members—the samurai-like vanguard Itsuka Shikabane, tech-genius Natalia Natasha Vasylchenko, troublesome Yasubee Yasu Morozumi, ex-gangster Gorou Shikabane, and multi-purpose robot Roboko Tsujii. With White Light, a powerful organization of justice, and the entire Japanese government against them, can Zvezda really dominate all humanity and let their light shine throughout the world?

Takashi Kamiyama is your typical mild-mannered high school student—polite, aloof, and pacifistic, with a slightly above-average IQ. But would your average high school student really enroll himself at the infamous Cromartie High School, known as a breeding ground for the toughest delinquents out there? Apparently so, as that is exactly what Takashi does, though for reasons he'd rather leave unmentioned. However, one thing is for sure: the hard-boiled rabbit in a den full of hungry lions is never going to have another dull day. And how could he, now that he's surrounded by mohawked punks, obnoxious robots, and... gorillas? And was that Freddie Mercury riding a horse down the corridor? Follow Takashi as he earnestly dedicates his new high school life to better his school's reputation while his classmates are hellbent on wreaking havoc.