The widowed Duchess of Malfi secretly marries her steward Antonio against the wishes of her two evil brothers, the Cardinal and Ferdinand. She and Antonio live happily for a while and pop out a few kids, but are eventually found out by Ferdinand's spy Bosola.
Once the cat's out of the bag about the Duchess's marriage and children, the brothers are on the warpath to destroy her and her family. The couple splits up, and the Duchess half (including two of the three kids) is captured and eventually executed by Ferdinand and his henchman-cum-spy, Bosola. Bosola, not loving what's gone down, resolves to save Antonio and do right by the dead Duchess.
After accidentally killing Antonio, the only thing left for Bosola to do is kill the Cardinal and Ferdinand (who has, in the meantime, turned in to a Grade-A, werewolf-y nutjob). He manages to off both the brothers, but gets killed in the process. The only surviving member of the family is the eldest child of the Duchess and Antonio, whom Antonio's friend Delio hopes to install as ruler in his mother's name.