Part 1: Episode 1 - 12
In the Roppongi district of Tokyo, high school student Shu Ouma encounters a wounded girl named Inori Yuzuriha, the vocalist of a popular internet group Egoist, taking refuge at his film club's workshop. Subsequently, members of the "Anti-Bodies", an elite GHQ unit tasked with containing the Apocalypse Virus by any means necessary, storm the workshop and arrest Inori for her involvement with a band of rebels called "Funeral Parlor".
After Inori's arrest, Shu follows the coordinates of Inori's robot to a drop zone where he meets Funeral Parlor's leader, Gai Tsutsugami, who asks him to safeguard a vial. As the Anti-Bodies begin attacking the Roppongi area in search of the vial, it shatters as Shu goes to rescue Inori when she becomes threatened by GHQ Endlave mechs. The vial contains the Void Genome, a powerful genetic weapon derived from the Apocalypse Virus that grants Shu the "Power of the King", an ability that allows his right hand to extract Voids, weapons of people's psyche given physical form. Shu then extracts Inori's Void and destroys the attacking Endlaves.
Upon deciding to join Funeral Parlor, Shu begins to fall in love with Inori, who bears a striking resemblance to his late sister, Mana. However, he deserts the group after killing a classmate's younger brother during one of his missions. In Shu's absence, Funeral Parlor attempt to steal from GHQ the meteorite that caused the Apocalypse Virus outbreak. In the process, Gai and his comrades fall into a trap as the Anti-Bodies ambush them with a "genetic resonance" broadcast that unleashes the Virus throughout Tokyo once again. Amidst the chaos, the Anti-Bodies' leader, Shūichirō Keido, seizes control of GHQ and orders all its forces to wipe out Funeral Parlor.
After learning his former comrades are in imminent danger of annihilation, Shu races to the center of Tokyo to rescue them. With the help of his classmates, he breaks through the barricade where they are being pinned down. Meanwhile, Inori begins to reverse the effects of the Virus through a resonance broadcast channeled by one of her songs. This sudden change in fortune proves only temporary when Yu, a mysterious boy possessing the "Power of the King", appears out of thin air and kidnaps Inori, causing the outbreak to resume with full force.
Shu finds Inori being held captive by Keido and Yu who are using her as a vessel for Mana's resurrection. They explain that Inori was created to provide a physical body for Mana's soul so she could give birth to a new human race once the existing population was destroyed by the Apocalypse Virus. Keido then proceeds to perform a "marriage" ritual intended to coerce Mana/Inori into accepting him as the father of her new progeny. Shu's repressed memories suddenly return, causing him to remember Mana was the first to be infected by the virus and how her mental breakdown resulted in the events of Lost Christmas. Shu also recalls from his past that Gai is none other than Triton, a childhood friend he first met ten years ago when Mana rescued him from the sea. With Gai's help, Shu frees Inori from Keido's grasp before stabbing the stasis pod containing Mana's dormant soul, seemingly killing her. Shu's actions save the world from the Virus, but Gai is killed in the process.
Part 2: Episode 13 - 22
Two weeks later, Shūichirō Keido has GHQ seal off the area surrounding Roppongi, now called Loop 7, before proceeding to systematically eliminate the inhabitants within. A large number of teenagers take refuge at Tennouzu High School along with Funeral Parlor members Shu, Inori, Ayase and Tsugumi. With food and vaccine supplies running low, Shu is elected the new student council president. Despite initially aspiring to provide just governance to those under his charge, his leadership becomes cynical and despotic once he concludes his refusal to adopt the social Darwinist "Voids-Ranking system" caused the death of his close friend and love interest, Hare Menjou.
Following a fierce battle with GHQ, Shu and the others manage to break out of Loop 7. However, upon their escape, a resurrected Gai suddenly appears and severs Shu's right arm before transferring the Void Genome to himself. In order to insure Shu's escape, Inori single-handedly holds off GHQ's forces until they overwhelm and capture her. Shortly thereafter, Shu's stepmother, Haruka Ohma, betrays GHQ and steals the third Void Genome. Upon making contact with Haruka, Shu injects himself with the new Void Genome before once again assuming command of Funeral Parlor to rescue Inori and free Japan from GHQ's tyranny once and for all.
After Gai broadcasts a message to the world not to interfere with GHQ's actions in Japan, he proceeds to help Yu and Keido resurrect Mana in Inori's body. It is ultimately revealed that GHQ is serving as a front for Da'ath, an ancient cult seeking to forcefully bring about mankind's evolution with the Apocalypse Virus. As the virus begins spreading across the planet from Tokyo Tower, Funeral Parlor and its allies launch a massive offensive against Tokyo Bay in a desperate bid to save the world from annihilation.
In the series' climactic final battle, Shu manages to defeat Yu and Gai while Funeral Parlor destroys GHQ's forces. After being cornered at gunpoint by Haruka, Keido chooses to commit suicide rather than surrender. A dying Gai explains to Shu that he helped Da'ath so Mana could fulfill her cursed role as the Fourth Apocalypse's Eve. With her role completed, he says that Mana is finally able to rest in peace.
