In a world where the light within people's hearts, known as Holo, can be gathered through a streaming app called HoloCast, a magical realm known as the HoloCast World exists. Six young women who normally work as HoloCast streamers are chosen to become magical girls named holoWitches. The central conflict arises from the Dreamend phenomenon, which occurs when individuals burdened by anxiety and stress lose their positive spirit, causing their souls to be pulled into the HoloCast World. The negative energy from these Dreamend victims gives birth to monsters called Collapsors. To defeat the Collapsors and save those who have fallen, the protagonists transform into their magical girl personas and fight to protect the hopes and dreams of the people.

The original team of holoWitches consists of Amane Kanata, Sakura Miko, Himemori Luna, Houshou Marine, Murasaki Shion, and Sakamata Chloe, each wielding unique weapons such as Kanata's powerful Guardian Arm gauntlet, Marine's energy blasting Gun Marina, and Luna's protective Caramel Parasol. They are guided in their mission by two fairy mascots named Aelu and Lagu. The team is visually divided into two subgroups: Team Luster, who wear white outfits, and Team Astra, who wear black.

The narrative is structured into distinct story arcs. The first story arc is titled The Magic of the Beginning. Following its conclusion and the departure of two original members, the project entered its second arc, The Magic of Promise. This arc sees the introduction of new magical girls, Shirakami Fubuki and Yukihana Lamy, who join the ongoing fight after being inspired by a former member to awaken their own powers and carry on the legacy of protecting the HoloCast World.