All of a sudden, they arrived: parasitic aliens that descended upon Earth and quickly infiltrated humanity by burrowing into the brains of vulnerable targets. These insatiable beings acquire full control of their host and are able to morph into a variety of forms in order to feed on unsuspecting prey. Sixteen-year-old high school student Shinichi Izumi falls victim to one of these parasites, but it fails to take over his brain, ending up in his right hand instead. Unable to relocate, the parasite, now named Migi, has no choice but to rely on Shinichi in order to stay alive. Thus, the pair is forced into an uneasy coexistence and must defend themselves from hostile parasites that hope to eradicate this new threat to their species.

The Four Cardinal Heroes are a group of ordinary men from modern-day Japan summoned to the kingdom of Melromarc to become its saviors. Melromarc is a country plagued by the Waves of Catastrophe that have repeatedly ravaged the land and brought disaster to its citizens for centuries. The four heroes are respectively bestowed a sword, spear, bow, and shield to vanquish these Waves. Naofumi Iwatani, an otaku, becomes cursed with the fate of being the Shield Hero. Armed with only a measly shield, Naofumi is belittled and ridiculed by his fellow heroes and the kingdom's people due to his weak offensive capabilities and lackluster personality. When the heroes are provided with resources and comrades to train with, Naofumi sets out with the only person willing to train alongside him, Malty Melromarc. He is soon betrayed by her, however, and becomes falsely accused of taking advantage of her. Naofumi then becomes heavily discriminated against and hated by the people of Melromarc for something he didn't do. With a raging storm of hurt and mistrust in his heart, Naofumi begins his journey of strengthening himself and his reputation. Further along however, the difficulty of being on his own sets in, so Naofumi buys a demi-human slave on the verge of death named Raphtalia to accompany him on his travels. As the Waves approach the kingdom, Naofumi and Raphtalia must fight for the survival of the kingdom and protect the people of Melromarc from their ill-fated future.

The final hour of the popular virtual reality game Yggdrasil has come. However, Momonga, a powerful wizard and master of the dark guild Ainz Ooal Gown, decides to spend his last few moments in the game as the servers begin to shut down. To his surprise, despite the clock having struck midnight, Momonga is still fully conscious as his character and, moreover, the non-player characters appear to have developed personalities of their own! Confronted with this abnormal situation, Momonga commands his loyal servants to help him investigate and take control of this new world, with the hopes of figuring out what has caused this development and if there may be others in the same predicament.

After the murder of her father, Ryuuko Matoi has been wandering the land in search of his killer. Following her only lead—the missing half of his invention, the Scissor Blade—she arrives at the prestigious Honnouji Academy, a high school unlike any other. The academy is ruled by the imposing and cold-hearted student council president Satsuki Kiryuuin alongside her powerful underlings, the Elite Four. In the school's brutally competitive hierarchy, Satsuki bestows upon those at the top special clothes called Goku Uniforms, which grant the wearer unique superhuman abilities. Thoroughly beaten in a fight against one of the students in uniform, Ryuuko retreats to her razed home where she stumbles across Senketsu, a rare and sentient Kamui, or God Clothes. After coming into contact with Ryuuko's blood, Senketsu awakens, latching onto her and providing her with immense power. Now, armed with Senketsu and the Scissor Blade, Ryuuko makes a stand against the Elite Four, hoping to reach Satsuki and uncover the culprit behind her father's murder once and for all.