Joutarou Kuujou and his allies have finally made it to Egypt, where the immortal Dio awaits. Upon their arrival, the group gains a new comrade: Iggy, a mutt who wields the Stand The Fool. It's not all good news however, as standing in their path is a new group of Stand users who serve Dio, each with a Stand representative of an ancient Egyptian god. As their final battle approaches, it is a race against time to break Joutarou's mother free from her curse and end Dio's reign of terror over the Joestar family once and for all.

Every 12 years, mercenaries who possess the highest caliber of brute strength, cunning wit, and deadly precision gather to participate in the Zodiac Tournament. Each warrior bears the name and attributes of one of the 12 animals of the Chinese zodiac. With their pride and lives on the line, they engage in vicious combat until only the victor remains. The 12th Zodiac Tournament begins in a desolate city, devoid of any evidence of the half million people who recently lived there. To raise the stakes, each warrior ingests a poisonous gem, thus setting a time limit on the tournament—and on their life. With one wish for the victor up for grabs, the Zodiac Warriors start their cutthroat battle for survival.

Violent misfortunes frequently occur around 16-year-old Yuuta Okkotsu, a timid victim of high school bullying. Yuuta is saddled with a monstrous curse, a power that dishes out brutal revenge against his bullies. Rika Orimoto, Yuuta's curse, is a shadow from his tragic childhood and a potentially lethal threat to anyone who dares wrong him. Yuuta's unique situation catches the attention of Satoru Gojou, a powerful sorcerer who teaches at Tokyo Prefectural Jujutsu High School. Gojou sees immense potential in Yuuta, and he hopes to help the boy channel his deadly burden into a force for good. Yet Yuuta struggles to find his place among his talented classmates: the selectively mute Toge Inumaki, weapons expert Maki Zenin, and Panda. Yuuta clumsily utilizes Rika on missions with the other first-year students, but the grisly aftermath of Rika's tremendous displays of power draws the interest of the calculating curse user Suguru Getou. As Getou strives to claim Rika's strength and use it to eliminate all non-jujutsu users from the world, Yuuta fights alongside his friends to stop the genocidal plot.

Idly indulging in baseless paranormal activities with the Occult Club, high schooler Yuuji Itadori spends his days at either the clubroom or the hospital, where he visits his bedridden grandfather. However, this leisurely lifestyle soon takes a turn for the strange when he unknowingly encounters a cursed item. Triggering a chain of supernatural occurrences, Yuuji finds himself suddenly thrust into the world of Curses—dreadful beings formed from human malice and negativity—after swallowing the said item, revealed to be a finger belonging to the demon Sukuna Ryoumen, the King of Curses. Yuuji experiences first-hand the threat these Curses pose to society as he discovers his own newfound powers. Introduced to the Tokyo Prefectural Jujutsu High School, he begins to walk down a path from which he cannot return—the path of a Jujutsu sorcerer.