Following the events of the Reze Arc, Denji, the young man who can transform into the Chainsaw Man, finds his life taking an unexpected and dangerous turn. Makima, his handler at Public Safety, broadcasts footage of Denji's battles as Chainsaw Man across the globe. This calculated move is meant to increase fear of the hero, but it has an immediate and violent side effect: it turns Denji into the world's most wanted target. Elite assassins and devil hunters from powerful nations, including the United States, the Soviet Union, China, and Germany, all converge on Tokyo. Their mission is to capture Denji's heart, the source of the Chainsaw Man's unique and fearsome power.

The setting shifts from the relatively contained conflicts of the previous arc to a sprawling, chaotic battleground across Tokyo. The city becomes a hunting ground where no one can be trusted, as assassins can be anyone, from a seemingly innocent civilian to a fellow public safety agent. This arc, which covers roughly eighteen chapters of the original manga, is defined by its relentless pace and the introduction of several formidable new characters. Among the most dangerous is Quanxi, a legendary and ruthless devil hunter from China, who is considered the strongest human fighter in the world. She is accompanied by her harem of fiend girlfriends, each with unique abilities. Another major threat is Santa Claus, a terrifying and grotesque devil hunter from Germany who operates as a hive mind and has formed a contract with the Doll Devil, allowing them to turn countless people into obedient, expendable soldiers.

As Denji is placed under the protection of a squad of Public Safety devil hunters, including Aki Hayakawa, Power, and new allies like the mysterious Hirofumi Yoshida, the situation escalates into a multi-sided war. The arc is notable for its shocking twists, one of which results in Denji and several key characters being transported to Hell itself. There, they face the Darkness Devil, a terrifying and powerful Primal Fear devil who embodies the most ancient and deep-seated terrors of humanity. This encounter pushes Denji and his allies to their absolute limits, with devastating consequences.

The International Assassins arc is a turning point in the Chainsaw Man story, moving beyond personal vendettas into a global conspiracy. It is a brutal and chaotic narrative that deepens the series lore, introduces the terrifying concept of Primal Fears, and forces Denji to confront enemies far more powerful and horrifying than any he has faced before. The arc sets the stage for the final, tragic events of the Public Safety Saga.