Young poetess Rose Elliot buys a book from a local antique dealer, a diary in Latin of an architect, E. Varelli. She learns of the Three Mothers, and believes her apartment building is one of their houses. She pleads her brother Mark, who is studying musicology in Rome, to come, because she is afraid. Mark's friend Sara reads her letter, which he left behind in class, and discovers the school is run by the Mater Lacrimarum, and is killed for this knowledge. The house of Mater Suspiriorum has already been destroyed, and by the time Mark arrives in New York City, he is investigating his sister's murder.

With Argento's trademark visual style, linked with one of his more coherent plots, Tenebrae follows a writer who arrives to Rome only to find somebody is using his novels as the inspiration (and, occasionally, the means) of committing murder. As the death toll mounts the police are ever baffled, and the writer becomes more closely linked to the case than is comfortable.

A psychic who can read minds picks up the thoughts of a murderer in the audience and soon becomes a victim. An English pianist gets involved in solving the murders, but finds many of his avenues of inquiry cut off by new murders, and he begins to wonder how the murderer can track his movements so closely.

A young American dancer travels to Europe to join a famous ballet school. As she arrives, the camera turns to another young woman, who appears to be fleeing from the school. She returns to her apartment where she is gruesomely murdered by a hideous creature. Meanwhile, the young American is trying to settle in at the ballet school, but hears strange noises and is troubled by bizarre occurrences. She eventually discovers that the school is merely a front for a much more sinister organization.

An ancient urn is found in a cemetery outside Rome. Once opened, it triggers a series of violent incidents: robberies, rapes and murders increase dramatically, while several mysterious, evil-looking young women coming from all over the world are gathering in the city. All these events are caused by the return of Mater Lacrimarum, the last of three powerful witches who have been spreading terror and death for centuries. Alone against an army of psychos and demons, Sarah Mandy, an art student who seems to have supernatural abilities of her own, is the only person left to prevent the Mother of Tears from destroying Rome.