The main character in Death is a Lonely Business is the narrator, who never gives his name; he is a modest writer, and a sensitive man, with a girlfriend who is a student in Mexico City. Critics feel that the narrator is, in fact, Bradbury himself, portrayed in a period of his life just before his marriage and his success with The Martian Chronicles. In his whodunit novel, a clear departure from his supernatural fiction, Bradbury's hero is both detective and a moral force that tries to conquer the macabre scene of an old amusement pier in Venice, where a morally dilapidated society dwells.

After discovering the body of an old ticket-taker in the canal near the site of the old amusement pier, the narrator solicits the help of a police detective friend named Elmo Crumley, whose interest is piqued because he is secretly a Romantic and the scene of death contains some elements of the Gothic.

But now the spirit-light took shape. Not only a hand, an arm, but an entire body sapped and loosely gesticulated, like and immense marionette, trapped in iron....And the ghost shapes are again. Within the cage, it was a dead man wanting out.

A would-be writer, Crumley finds unusual characters in the older residents in the area, including aging film stars and two opera divas. The narrator donates the title of "Death is a Lonely Business," the words of an old man on the trolley on the night of the discovery of the first victim. Ironically, the young writer becomes the one to resolve the case and the detective publishes his manuscript.