Jérôme was born Roland Buonaparte in Ajaccio, Corsica as the eighth and last surviving child, fifth surviving son, of Carlo Buonaparte and Letizia Ramolino. He was a younger brother of Joseph Bonaparte, Napoleon Bonaparte, Lucien Bonaparte, Elisa Bonaparte, Louis Bonaparte, Pauline Bonaparte and Caroline Bonaparte.

He served with the French navy before going to the United States. On December 24, 1803, Jérôme married Elizabeth Patterson (1785-1879), daughter of Baltimore merchant William Patterson and his wife Dorcas Spear. Napoleon annulled their marriage but a son, Jérôme Napoleon Bonaparte was born in Camberwell Grove, Camberwell, London, England.

Made King of Westphalia, the short-lived realm created by Napoleon from the states of northwestern Germany (1807-1813), with its capital in Cassel, Jérôme married the second time to Catharina of Württemberg, with whom he had another son, Napoléon Joseph Charles Paul Bonaparte (1822-1891), also known as "Prince Napoleon" or "Plon-Plon". Their second child, a daughter, the Princess Mathilde Bonaparte, was prominent during and after the Second French Empire as a hostess. After his own kingdom was dissolved, he was granted the title of Prince of Montfort by the King of Württemberg.

After Emperor Napoleon's exile, Jérôme moved to Italy where he married Giustina Pecori-Suárez, the widow of an Italian nobleman. When his nephew, Prince Louis Napoleon, became President of the French Republic in 1848, Jérôme was made governor of Les Invalides, Paris, the burial place of his famous elder brother Napoleon I of France. He later became marshal of France and president of the Senate in his nephew's regime, and was confirmed in the title of prince français.

Jérôme Bonaparte died on June 24, 1860 at Villegenis, France (today Massy in Essonne). He is buried in Les Invalides, Paris.