Pier Francesco Orsini, the Duke of Bomarzo, a stunted hunchback, drinks what his astrologer Silvio de Narni claims to be a magic potion that will grant the Duke immortality. However, the drink turns out to be poisoned. After the poison starts to work, Bomarzo begins to recall his life in a series of flashbacks.

His father drags the young Pier Francesco into a room where a large skeleton dances and haunts him. Later, his father falls in battle. In Florence, the young, virginal Pier Francesco goes to see to the courtesan Pantasilea. However, he sees his image in her room of mirrors, to his disturbance.

Pier Francesco's brother Girolamo falls from a cliff and dies, and Pier Francesco becomes the new Duke of Bomarzo. He meets Julia Farnese, who prefers Bomarzo's brother Maerbale, to his anger. At a dance festival, the Duke experiences various dreams. While courting Julia, he spills a glass of red wine on her dress, which he interprets as a premonition of death.

Bomarzo and Julia eventually marry, but Bomarzo then becomes impotent. As time passes, the Duke creates large stone sculptures on his estate, symbolic of his tortured feelings. He starts to think that Julia is betraying him with Maerbale. The Duke orders his slave Abul to kill his brother.

The astrologer Silvio mixes the magic potion as Bomarzoâ??s nephew Nicolas watches. Nicolas then poisons the drink. After he drinks the potion, the Duke dies.