As Ganta Igarashi and his classmates plan for a class trip to Deadman Wonderland, a privately owned prison that also serves as an amusement park, a mysterious red man appears and changes their lives forever.

Ganta learns from a fellow inmate, Yō Takami, that in order to have a decent meal in the prison, he needs to earn Cast Points. He learns of a 'Dog Race' in which he can win a big prize, which he and Shiro decide to enter. In the lockerroom, they encounter a fierce inmate named Kazumasi Kouzuma who drives fear into the others until the warden silences him. Ganta soon learns that in order to avoid being killed by a poison, he needs to eat an antidote known as Candy, which was secretly stolen from his bag by Yō the other day. Ganta realises that in order to survive, he needs to win the race in order to purchase a new one, but he soon learns the course is littered with actual death traps. Thanks in part to Shiro's innocent manner, Ganta and Shiro make it to the final stage against Kasumasi where they have to hold onto a ball and avoid falling into a spike pit. Ganta decides to stand up to Kazumasi, who eventually falls to his death. In the closing moments of the round, Ganta is forced to sacrifice the ball, and the prize money, in order to keep Shiro from falling and keep their promise of eating the runner up prize together.

Put in charge of observing him by the promoter, Tsunenaga Tamaki, Yō gives Ganta a piece of Candy so he can keep living, unaware that he's putting him in his debt. Meanwhile, the red man, known as the Wretched Egg, breaks lose and appears before Ganta. Ganta tries attacking him using his own abilities, before the Wretched Egg escapes and Ganta falls unconscious. After waking up, Ganta hears from the other witnesses that they keep Wretched Egg locked up in the G-Block of the prison, so he and Shiro head towards there. Deeming him dangerous, Captain Makina puts the facility on lockdown and sends a fierce security robot after Ganta. As it approaches them, Ganta and Yō follow Shiro into a secret passage leading to the G-Block. As Shiro confronts the robot, it is destroyed by the arrival of another inmate with the same powers as Ganta.

Believing him to be the red man, Ganta attacks the strange inmate, known as Senji "Crow" Kiyomasa, but falls at a disadvantage against the blades he can form with his blood. After learning the nature of his power, The Branches of Sin, Ganta launches a counterattack, though soon realizes he is not the red man, but one of several 'Deadmen' with that power. Crow tries to attack Ganta again, but finds himself weak against Shiro before a special unit appears, tranquilising Ganta and Crow and taking Shiro and Yō to an empty corridor. As Ganta is examined, he comes face to face with Tamaki, who reveals he rigged Ganta's jury verdict to get him sent to Deadman Wonderland before revealing Ganta will face off against Crow in a battle the next day, tempting him with the prospect of coming face to face with Wretched Egg. As Ganta is tortured with footage of what a Corpse Carnival entails, Makina decides to confront the director concerning the mysteries of Block G.

Ganta is thrusted into his Corpse Carnival match with Crow and is at a disadvantage as his projectiles use too much blood and cause him to develop anemia. As he becomes helpless, he recalls memories of Shiro and manages to stand back up, using the environment to get a hit on Crow. After escaping from the corridor, Yō and Shiro head towards G-Block after Yō hears the whereabouts of a women he is searching for. After Ganta recovers from his victory, he is horrified to find that Crow is forced to have one of his eyes removed as a result of losing. As Yō uses Shiro as a diversion so he can escape on his own, he bears witness to her true destructive ability, as she herself has the Branches of Sin.

As Shiro falls unconcsious and is picked up by some strange men whilst Yō continues his way to G-Block, Ganta meets a girl named Minatsuki, another Sin user who had killed her abusive father. Ganta offers to help Minatsuki escape, but soon learns she is his opponent in the next Corpse Carnival. When the match begins, Minatsuki's personality changes completely and attacks with her whip-like Branches of Sin, revealing she had manipulated him into taking an injury prior to the match. However, Yō appears, revealing Minatsuki to be his little sister, saying that he plans to gain enough Cast Points to buy her freedom before entering the arena. Minatsuki tries to manipulate Yō against Ganta, but he turns on her instead, having learnt the truth behind his father's death. Minatsuki captures Yō and uses him as a human shield against Ganta, revealing she has shown hatred ever since her mother left her for dead during the Red Hole incident. Ganta manages to disable one of her whips and free Yō, before knocking her out with a headbutt, winning the match.

After a strange quake occurs, during which Yo rushes to keep Minatsuki from harm, Ganta starts to remember things about Shiro, who is revealed to be the Wretched Egg. As Ganta recalls his childhood with Shiro, Yo can't bring himself to mention what he had seen her do. As Yo goes to recover the casts that were stolen from him, he learns from Tamaki that casts can't be used to reduce the sentences on G-Block inmates and is attacked by Genkaku, part of an Anti-Deadman force known as the Undertakers. Meanwhile, Ganta meets Nagi "Owl" Kengamine and Karako Koshio, members of a Deadman group known as Scar Chain wanting to destroy Deadman Wonderland, who invite him to join their gang. As Minatsuki goes through her penalty game, Nagi arranges it so that she only loses her hair. Just then, Genkaku appears and attacks Ganta and the others.

Ganta is saved by the arrival of Shiro, who is back under control by the lullaby, to which Genkaku decides to retreat. Afterwards, Ganta is introduced to the other members of Scar Chain, who are plotting to expose Deadman Wonderland's secrets an inspection week, which Makina also plans to take advantage of to find out what secrets are being hidden from her. However, Ganta becomes a little distrustful when his claims of his Branches of Sin being stopped by Genkaku differ from what the security cameras show and takes his leave. Ganta later learns from Crow about how Genkaku killed Nagi's wife, later hearing from Nagi about how each member of Scar Chain has their own ideas of freedom. As Ganta promises to take Shiro on a ferris wheel when they escape someday, it is shown that one of Scar Chain's members, Binjou Rokudo, is a double agent for the Undertakers. Ganta decides to join Scar Chain, who begin their operation to leak information about the Deadmen to the outside world. As Nagi and Rokudo go to the security room, Ganta and the others are chased by an acid spewing robot, to which Karako opts to stay behind to save the others.

After recalling the time she joined Scar Chain, Karako defends herself from the acid spewing robot and destroys it, falling down with it. Meanwhile, Nagi is betrayed by Rokudo and confronted by an Undertaker named Hibana Daida, who uses a special weapon to neutralize his Branches of Sin. As Hibana starts slicing off bits of Nagi's flesh, he provokes her into chopping off his arm, giving him the opportunity to activate the elevator Ganta's group needs to take. However, Ganta's group is confronted by Genkaku and his men, leaving only Ganta and a few others left alive to carry the chip containing the information. Whilst bleeding to death, Nagi makes a call to the hideout, which is heard by Shiro who catches up to Ganta and throws the chip, which was actually a bomb, into a fire.

Ganta becomes angry at Shiro for throwing away the data chip, telling her he never wants to see her again. Meanwhile, Mikuni investigates Tamaki's office, overhearing a conversation between him and the Defense secretary concerning the Deadmen. As Karako and the others discuss their next plan, Rokuro appears and reveals the data chip was actually a bomb he had made before announcing that the group is being held hostage unless Nagi agrees to become an Undertaker. As Rokuro decides to execute Ganta first, Crow appears on the scene, managing to fight back against the Undertakers using sonic blasts. As Shiro laments her situation with Ganta, she meets Toto "Mockingbird" Sakigami, the one who told her about the bomb.

Detesting his weak self, Ganta asks Crow to teach him how to use his Branches of Sin to fight. Meanwhile, Karako attempts to infiltrate the Undertakers by disguising herself as a guard. As Toto appears before Ganta and Crow during their training session, Shiro, who gets drunk off of liquer sweets, appears before Genkaku, who also discovers Karako. Just as Ganta manages to produce a blood bullet that can break the sound barrier, Genkaku announces his capturing of Karako and Shiro. Despite being low on blood, Ganta rushes to where Genkaku, Karako and Shiro are, but is confronted by Nagi, who had been broken by Genkaku into a raging demon.

As Nagi goes on a rampage on all the guards, Ganta stands to protect Shiro, taking all of his punches and trying to reason with him. As Nagi starts to come to his senses thanks to the bell Karako wears reminding him of his friends, Karako is suddenly stabbed by Genkaku. Nagi stands to protect his friends but is shot by Genkaku, who begins killing the other guards, whilst Ganta starts being poisoned due to not having any Candy in a while. Hibana tries to escape but is killed by Toto, who had managed to obtain Crow's abilities after drinking his blood. As Shiro enters Wretched Egg mode, the stone in Ganta's chest glows and blasts a powerful shot, with Nagi holding Genkaku in place as they are both taken out. Before passing on, Nagi gives Ganta his last piece of Candy. As Karako and some others escape, Ganta decides to stay behind so he can protect his friends.