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.

The maid Lilith, hired to look after young Yuuri and his family's mansion, seems highly suspicious: she is too good to be true. Every dish she serves turns out to be delicious, the whole residence sparkles after she cleans it, and all the clothing has given off a pleasant scent since she started doing the laundry. Furthermore, her devilishly beautiful eyes only serve to heighten Yuuri's suspicions. Is Lilith perhaps a witch or a sorcerer? Yuuri cannot figure it out. But despite his misgivings, Yuuri has to live with Lilith as he tries to unravel the mystery behind her otherworldly charm.

Tooru Kirishima's notoriety is spread far and wide in the underworld. He is most commonly known as "The Demon of Sakuragi"—a man who is not afraid to resort to violence if deemed necessary. After almost jeopardizing a peace treaty, his boss tasks him with the most difficult job he has ever had: taking care of seven-year-old Yaeka Sakuragi—the boss' precious daughter—so that Tooru understands what it means to be responsible for another life. At first, the two do not seem to meet eye to eye, as Tooru has no clue on how to communicate with Yaeka, and the young girl is not used to expressing her emotions. However, as time goes on, they come to understand each other despite their differences. The fearsome right-hand man of a yakuza boss and the child he must protect are about to learn that family is not always bound by blood.

After a fatal encounter with a truck, Takafumi Takaoka's uncle, Yousuke "Ojisan" Shibazaki, lies comatose for 17 years. When he finally regains consciousness, Ojisan begins to ramble in a foreign tongue and reveals that he had been transported to a magical world called Gran Bahamal. Takafumi dismisses his uncle's claims as nonsense until an incantation makes a cup of water hover in the air. In a flash of brilliance, the pair creates a YouTube channel to showcase Ojisan's magical abilities. The responsibility now falls on Takafumi's shoulders to acquaint Ojisan with everything that has transpired during his absence, including getting him up to speed with the internet, new technology, and surprisingly, the outcome of the '90s console war—the result of which was especially distressing for a hardcore SEGA fan. With Ojisan's wisdom from his other world experiences, they grow their YouTube channel and tackle online comments and trolls. The journey of this uncle-nephew duo promises to be anything but conventional.