Ichigo Momomiya is excited to start high school and fall in love. She is in luck when she meets the popular and good-looking Masaya Aoyama, and she immediately develops a crush on him. When Ichigo learns that Aoyama is passionate about the environment, she seizes the chance to ask him out thanks to some tickets to an exhibition about endangered animals. During their date, Ichigo is struck by a mysterious light and faints. Waking up to the sight of Aoyama, she remains unharmed—but they both must escape from a giant rat-like creature after it injures Aoyama. To save her crush, Ichigo awakens her powers and transforms into a heroine with the skills of a cat. After she defeats the monster, researchers Ryou Shirogane and Keiichiro Akasaka explain that Ichigo was chosen to become a part of the Mew Project: a group of five magical girls whose DNA has been infused with those of certain endangered species. Now, Ichigo must find the rest of her teammates to defeat the Chimera Anima—beings infected by aliens who want to take over the world—before it is too late.

Alto Goldfilled, a diligent student at the Ortigia Academy of Magic, aspires to become a powerful sorcerer. But he is unable to become one as, despite his excellent grades and strong commitment to his studies, he fails his summoning class. With the threat of repeating a year hanging over his head, Alto tries following an old, worn-out grimoire in a desperate attempt to resolve his situation. To his surprise, he succeeds and summons a powerful demon named Vermeil. As a sign of gratitude for releasing her, Vermeil agrees to become Alto's familiar, sealing their relationship with a deep kiss. Little does Alto know what else he is capable of and what Vermeil's past hides.

The story takes place shortly before Cartaphilus took a nap and Chise became an auditor at the academy. Elias and his friends help Chise prepare for the academy, where in the middle of everyday life, Spriggan visits the mansion on a spooky horse with the words, "The appearance of the ghost hunting association is unusual this time." Gabriel, an ordinary boy who just moved from London, was bored of his environment of parting with friends, being in an unfamiliar location, and everything else. Sitting by the window and glancing beyond, he spotted a purple smoke and decided to chase after it, looking to escape his boredom. Though it should not, the world of the boy begins to converge with the wizards, who live on the other side behind a thick veil.

In the world of Remnant, humans and Faunus—human-animal hybrids—carry on their everyday lives despite the omnipresent threat of the monstrous Grimm. Dedicated Huntsmen and Huntresses battle Grimm with both customized weapons and their own "Semblances," unique abilities derived from the energy of one's soul. Some warriors also utilize a crystallized energy propellant, "Dust," to bestow their weapons with elemental properties. In this dangerous line of work, rigorous training is required to stay alive. To that end, each of Remnant's four Kingdoms have established schools to properly groom children holding aspirations of becoming licensed Huntsmen. At Beacon Academy in the Kingdom of Vale, a promising group of future Huntresses make their debut as Team RWBY. Ruby Rose, Weiss Schnee, Blake Belladonna, and Yang Xiao Long each come from different backgrounds and often butt heads as a result. However, when they cooperate, they are a formidable force who have even attracted the attention of Beacon's headmaster Professor Ozpin. Alongside fellow students such as those in Team JNPR, the young prodigy Ruby and her friends engage in adventures which pit them against an extremist Faunus group known as the White Fang. Every explosive encounter also brings them closer to the true villains orchestrating conflicts from the shadows.