Seven years after humanity was devastated by a major disaster, a beacon of science and prosperity rises in Kamitsubaki City. But lurking in its shadows are Tesseractor, monsters born from human darkness. Only the Witchling, five girls with voices that wield magic, stand against them. With every note, they fight, not just to protect the peace of the city, but to heal a broken world.

Years after an ancient evil was salvaged from the depths of the sea, Joutarou Kuujou sits peacefully within a Japanese jail cell. He's committed no crime yet demands he not be released, believing he's been possessed by an evil spirit capable of harming those around him. Concerned for her son, Holly Kuujou asks her father, Joseph Joestar, to convince Joutarou to leave the prison. Joseph informs his grandson that the "evil spirit" is in fact something called a "Stand," the physical manifestation of one's fighting spirit which can adopt a variety of deadly forms. After a fiery brawl with Joseph's friend Mohammed Avdol, Joutarou is forced out of his cell and begins learning how to control the power of his Stand. However, when a Stand awakens within Holly and threatens to consume her in 50 days, Joutarou, his grandfather, and their allies must seek out and destroy the immortal vampire responsible for her condition. They must travel halfway across the world to Cairo, Egypt and along the way, do battle with ferocious Stand users set on thwarting them. If Joutarou and his allies fail in their mission, humanity is destined for a grim fate.

The year is 1999. Morioh, a normally quiet and peaceful town, has recently become a hotbed of strange activity. Joutarou Kuujou, now a marine biologist, heads to the mysterious town to meet Jousuke Higashikata. While the two may seem like strangers at first, Jousuke is actually the illegitimate child of Joutarou's grandfather, Joseph Joestar. When they meet, Joutarou realizes that he may have more in common with Jousuke than just a blood relation. Along with the mild-mannered Kouichi Hirose and the boisterous Okuyasu Nijimura, the group dedicates themselves to investigating recent disappearances and other suspicious occurrences within Morioh. Aided by the power of Stands, the four men will encounter danger at every street corner, as it is up to them to unravel the town's secrets, before another occurs.

While helping out at an anime convention to promote his city, high school student Kakeru Niimi is caught up in a sudden earthquake. During the emergency, he ends up entering a shrine where he sees a peculiar relic shatter. The very next day, his classmate Miyako Kujou, who was cosplaying at the event, worries that she has been cursed as a result of the earthquake, but Niimi brushes her suspicions off. However, Niimi's mind changes when he discovers that various people have gained supernatural powers in the city—and that some have started using them for nefarious purposes. Fortunately, Niimi is not alone: he is joined by Miyako, his sister Sora, and a cold girl named Noa Yuuki, who have all awakened to their own abilities. If the group wants to keep their hometown safe, they must strive to prevent any future incidents while unraveling the mystery behind it all.