The ExWire of True Cross Academy are beset with shock and fear in the aftermath of discovering that one of their own classmates, Rin Okumura, is the son of Satan. But for the moment, they have more pressing concerns than that of Rin's parentage: the left eye of the Impure King, a powerful demon, has been stolen from the academy's Deep Keep. After an attempt is made to steal the right eye in Kyoto as well, Rin and the other ExWires are sent to investigate the mystery behind the Impure King and the ultimate goal of the thief. While this mission has them cooperating for the time being, Rin has never felt more distant from his fellow exorcists. In his attempt to reconcile with them, he undergoes specialized training to control his dark power. However, when the right eye is stolen not long after their arrival, the unthinkable threat of a traitor amongst them leaves them in need of all the power they can get.

The ordinary life of 17-year-old otaku Hajime Nagumo is disrupted when he and his classmates are summoned to a fantasy world and tasked with saving mankind. While his classmates are gifted with impressive abilities useful in combat, Hajime is belittled for only gaining an inferior transmutation skill that lacks any real offensive power. During an expedition in the Great Orcus Labyrinth, Hajime is betrayed by one of his classmates, plummeting him to the bottom of an abyss. Though he survives the fall, Hajime is faced with menacing monsters and misfortunes that send him spiraling into a grim nightmare. Desperate to live and return home one day, he resolves to fight for his survival—only to meet an imprisoned vampire he names Yue, who is also seeking to escape the labyrinth. Taking an interest in him, Yue and a few others along the way accompany Hajime on his journey to find a way back home, while steadily transforming from commonplace to the world's strongest.

Edo is a city that was home to the vigor and ambition of samurai across the country. However, following feudal Japan's surrender to powerful aliens known as the Amanto, those aspirations now seem unachievable. With the once-influential shogunate rebuilt as a puppet government, a new law is passed that promptly prohibits all swords in public. Enter Gintoki Sakata, an eccentric silver-haired man who always carries around a wooden sword and maintains his stature as a samurai despite the ban. As the founder of Yorozuya, a small business for odd jobs, Gintoki often embarks on endeavors to help other people—though usually in rather strange and unforeseen ways. Assisted by Shinpachi Shimura, a boy with glasses supposedly learning the way of the samurai; Kagura, a tomboyish girl with superhuman strength and an endless appetite; and Sadaharu, their giant pet dog who loves biting on people's heads, the Yorozuya encounter anything from alien royalty to scuffles with local gangs in the ever-changing world of Edo.

After his relationship with Eris Boreas Greyrat reaches new heights, Rudeus Greyrat is ecstatic. Unfortunately, his joy is short-lived, as Eris suddenly abandons him to embark on her own journey. Believing that Eris has lost all interest in him, a heartbroken and depressed Rudeus sets forth to the Northern Territories. With his sole goal being to locate his mother on the vast continent, Rudeus wonders if persisting through daily life is worth the pain, falling into a robotic routine as he endlessly ruminates on his lost love. However, the dangers of the North soon prove that one cannot survive with a dulled mind. While on a quest with the party Counter Arrow, with whom he recently became acquainted, Rudeus has a brush with death—an experience that forces him to finally snap out of his despair. With his newfound teammates, Rudeus rediscovers the pleasure of daily adventuring and moves forward with his original goal of living his second lease on life to the fullest.