Webster's source for The Duchess of Malfi is the real-life story of the Duchess of Amalfi, a woman named Giovanna. This real duchess was the daughter of the King of Naples's half-brother and was married at the age of twelve to the man who would three years later become the Duke of Amalfi. She had one child by him, born five months after his death. She was widowed at age nineteen, then secretly married her steward, Antonio Beccadelli of Bologna, and had three children with him. Her brothers were said to have had her murdered when they found out about the marriage.

Webster would likely have known this story from a book called The Palace of Pleasure, a group of tales that was assembled by William Painter in 1567.

Webster's story tracks closely with the historic narrative of the Duchess of Amalfi, though her suspected murder by her brothers has never been confirmed. Webster, from a lower-middle-class English family, would have well understood the class issues involved in the duchess marrying a steward.

The real-life story, full of murder and intrigue, would have been attractive to Webster at a time when bloody revenge dramas were in vogue and likely to be profitable by bringing in large audiences looking for a thrill.