The action takes place at or near the estate of the Duchess at Malfi. By the end of the opera, every principal character in the tragedy has met a violent end, the good and innocent along with the evil and deranged. Their ends are hastened by the murder of the Duchess herself, and the opera opens with Ferdinand’s dying words: “My sister, oh, my sister – there’s the cause on’ t’ ‘, followed by a descriptive prelude.

Daniel de Bosola seeks remuneration from the Cardinal, for whom he has committed murder. He is spurned. The Duchess of Malfi, a young widow, is enjoined by her twin-brother, Ferdinand, the Duke of Calabria, and their elder brother, the Cardinal, not to consider future matrimony. The Cardinal is concerned with politics, but Ferdinand, who lusts after his twin, cannot bear that any other man shall touch her.

The Duchess has fallen in love with Antonio Bologna, the master of her household, and, aided by her attendant Cariola, she has wooed him into a secret marriage.

Ferdinand, leaving for the wars, is persuaded by the Cardinal to set Bosola to spy upon their sister. Bosola enters the Duchess’ employ as Master of her Horse.

The Duchess is pregnant by Antonio, but so far she has managed to hide the fact of her marriage-solely from fear of her brothers’ wrath. Bosola, sure of his case, tempts the Duchess’ fevered appetite with “apricocks” (apricots). Her lust for the over-ripe fruit gives her away to Bosola’s sharp eye. The birth is brought on prematurely and Antonio stages a false alarm of poison and robbery to explain the cries from the Duchess’s bedroom and to confine the gentlemen of the Court to their chambers.

Bosola is not deceived; when Ferdinand receives the news of the birth, the madness of his character begins its headlong rush towards dissolution. He returns to the court of Malfi at the height of a ball and Bosola effects his introduction into the Duchess’s bedchamber. Antonio has just left her, but the Duchess, unaware of this fact, continues to ask and speak as if he was still with her, little knowing that she is in fact addressing her brother. Her dreadful understanding comes too late.

She flees with Antonio and their child to take sanctuary from Ferdinand’s mad wrath in the monastery at Ancona, disguised as pilgrims. Bosola alerts the Cardinal who arranges that they shall be banished from Ancona. Antonio and the child escape, the Duchess is taken.

The Duchess is confined with her faithful Cariola in the prison of her own castle. Ferdinand sends a Masque of Madmen to discomfort her further and to cause her to doubt her own sanity. She, however. maintains her dignity and her serenity: believing her husband and child to have been murdered, she awaits death calmly herself.

This comes with Bosola who, his own sense of integrity overcoming the corruption of his mission, refuses to appear before the Duchess as himself. He comes as an old monk, with coffin and bible. He strangles the Duchess.

Ferdinand. at whose command this murder has been committed, now blames the murderer. He embraces the corpse of his sister and the collapse of his sanity is completed. The Doctor pronounces him to be mad as he rants about the palace, lewdly consorting with his sister’s shroud.

The Cardinal commands Bosola to seek out his sister’s husband and to destroy him. Bosola, finding himself commanded to destroy the only people for whom he has any respect, refuses and resolves to destroy the perpetrators.

Antonio is murdered among some ancient ruins where the voice of the Duchess is unable to warn him of his doom. He dies.

In the final bloody holocaust of reckoning, murderer turns against master and brother against brother. The Cardinal’s own duplicity works against him; Ferdinand’s sorrow and madness destroy them both, and Bosola along with them: My sister, oh, my sister! there’s the cause on’ t.