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Francis was born in Naples, the son of Ferdinand I of the Two Sicilies and Maria Carolina of Austria. He married Clementina, daughter of the emperor Leopold II, Holy Roman Emperor, in 1796, and at her death Isabella, daughter of Charles IV of Spain. After the Bourbon family fled from Naples to Sicily in 1806, and Lord William Bentinck, the British resident, had established a constitution and deprived Ferdinand I of all power, Francis was appointed regent (1812).
On the fall of Napoleon his father returned to Naples and suppressed the Sicilian constitution and autonomy, incorporating his two kingdoms into that of the Two Sicilies (1816); Francis then assumed the revived title of duke of Calabria. While still heir apparent he professed liberal ideas, and on the outbreak of the revolution of 1820 he accepted the regency apparently in a friendly spirit towards the new constitution. But he was playing a double game and proved to be the accomplice of his father's treachery.
On succeeding to the throne in 1825 he cast aside the mask of liberalism and showed himself as reactionary as his father. He took little part in the government, which he left in the hands of favourites and police officials, and lived with his mistresses, surrounded by soldiers, ever in dread of assassination. During his reign the only revolutionary movement was the outbreak on the Cilento (1828), savagely repressed by the marquis Delcarretto, an ex-Liberal turned reactionary.