After destroying Earth many years ago, the alien race Gauna has been pursuing the remnants of humanity—which, having narrowly escaped, fled across the galaxy in a number of giant seed ships. In the year 3394, Nagate Tanikaze surfaces from his lifelong seclusion deep beneath the seed ship Sidonia in search of food on the upper levels, only to find himself dragged into events unfolding without his knowledge. When the Gauna begin their assault on Sidonia, it's up to Tanikaze—with the help of his fellow soldiers and friends Shizuka Hoshijiro, Izana Shinatose, and Yuhata Midorikawa—to defend humanity's last hope for survival, and defeat their alien foes. Sidonia no Kishi follows Tanikaze as he discovers the world that has been above him his entire life, and becomes the hero Sidonia needs.

Ten years ago, a fairy by the name of Daisy appeared and asked the child Eiji Hoshimiya what his one and only wish was. Although his wish remains a mystery, the consequences were catastrophic. In an event called the Great Destruction, the world started to fall apart as everything collapsed and countless people died. Now, Eiji is a high school student whose only concern is his sick sister. He does not remember what he wished for; all that he remembers is that his wish caused the Great Destruction. In the years since that event, thousands of other people have also received abilities to make their heart's desire come true. These people called Orders are believed to be evil and are hated by the general public. However, some of these Orders are after Eiji's life in vengeance for those that he killed. Will Eiji be able to survive the numerous assassination attempts? And the biggest mystery of all: what did he wish for, and what were his intentions in wishing for something that caused so much desolation?

Hino Akiharu lost his parents when he was small and was adopted into his uncle's family. He didn't want to be a burden on his uncle's family and decides to enter a free boarding school as a butler, Hakureiryou high school. However, his delinquent boy-like appearance frightens the girls, who make up the majority of the students. Unable to get along with the classmates, Akiharu meets his childhood crush Saikyou Tomomi.

On live television, Mina Tepes, the ruler of all vampires, reveals the existence of her species to the world and states her plan to build a sanctuary in Japan for vampires, called the Vampire Bund. Using her family's wealth to pay off the nation's debt, they have agreed to let her build this safe-haven for her fellow creatures of the night. But not everyone is so easily swayed by Mina's influence, as her announcement brings about conflict with humans who believe that the queen's quest for peace is a façade. Akira Kaburagi does not believe in vampires and gets uneasy whenever they are brought up, although he has yet to realize why. Apart from suffering a head injury a year ago, he lives on blissfully until he meets Mina. She triggers within him memories of a life he had long forgotten, and he soon begins protecting her without understanding why. But Akira's secret is far stranger than he could have ever thought possible—he discovers that he is a werewolf, sworn from birth to protect the vampire queen, even if it costs him his life. Now, as these two dance a rondo of death in the Vampire Bund, Mina and Akira find out just how deep their bond goes.