The novel unfolds as a murder mystery, revealing the planned revenge killing of a young man named Santiago Nasar by the Vicario brothers. They believe Santiago has dishonored their sister, Angela, by taking her virginity before her marriage to another man. Despite the impending murder being common knowledge within the small Colombian town, a series of coincidences and misunderstandings prevent anyone from intervening, leading to Santiago's tragic and foretold demise. The narrative explores themes of honor, fate, and the collective responsibility of a community.

This novel is a dark and gripping exploration of life in Medellín, Colombia, during the height of the drug wars. The protagonist, a middle-aged writer, returns home after many years abroad, only to find his city ravaged by violence and death. He falls in love with two teenage assassins, who guide him through the underworld of the city, exposing him to the brutal realities of life in a place where human life has lost all value. The story is a bleak commentary on the devastating effects of drug trafficking and political corruption on society.