The setting is modern-day Japan. A seventeen-year-old delinquent named Jotaro Kujo has acquired the unique ability to manipulate a powerful vision called a Stand. Due to a connection dating back a hundred years, DIO is after Jotaro's life. One morning, a green tentacle attacks Jotaro on his way to school. The injured Jotaro then sees a boy offering him a handkerchief. The boy identifies himself as Noriaki Kakyoin, a transfer student, before walking away. When Jotaro stops by the infirmary to receive treatment for his injuries, Kakyoin uses a female doctor to challenge him to a fight!
Jotaro, Avdol, Joseph, Kakyoin, and Polnareff continue their journey to Cairo. A strange thing occurs when they arrive in Calcutta, India: an eerie melody can be heard over the hustle and bustle of the city. It is that of an old man playing an organ. The melody is not a pleasant one, however, but an evil one that drives people's hearts berserk. The old man uses his Stand of sound to control Kakyoin first, then Polnareff, Avdol, Joseph, and even Jotaro!
Jotaro, Joseph, Avdol, Kakyoin, and Polnareff continue their journey to Cairo, where their nemesis DIO resides. During their stay in Calcutta, two assassins sent by DIO await them: the cruel and despicable J. Geil, whose Stand hides itself within mirrors, and Hol Horse, a cowboy whose Stand takes the form of a gun. Being the man who killed Polnareff's sister, J. Geil provokes Polnareff, causing him to confront the killer against the advice of his comrades!
Avdol is dead! He is lethally shot by Hol while trying to save Polnareff from his and Geil's trap. Upon learning of Avdol's death, Jotaro, Joseph, Polnareff and Kakyoin each pursue their enemies. Hol and Geil also decide to fight separately, taking advantage of the fact that Jotaro's group is divided. With Jotaro up against Hol Horse, and with Polnareff and Kakyoin fighting J. Geil, a fierce battle to the death begins. Will Polnareff succeed in taking his revenge?
Finally, Jotaro and his friends arrive in Cairo and enter DIO's Mansion, though they lose their friends Avdol and Iggy along the way. However, DIO attacks them in an unexpected manner, killing Kakyoin and mortally wounding Joseph. DIO's Stand, The World, is a terrifying Stand that can freeze the entire world's time for several seconds to attack. Jotaro and Polnareff struggle against DIO, but their desperate resistance succeeds in wounding him!
DIO, wounded, devises a secret plan to restore his own life force. By successfully tricking Jotaro, DIO regains his vitality and pushes him to the brink of death—and as his power grows, DIO's damaged brain goes more and more insane. As his consciousness begins to fade, Jotaro hears the voices of his mother Holy, Joseph, and his dead comrades. However, over the course of the battle, Jotaro has learned how to stop time himself. And so, Jotaro lets out one final burst of anger.