Radcliffe was born as Ann Ward in Holborn. Her father was William Ward, a haberdasher; her mother was Ann Oates. At the age of 22, she married journalist William Radcliffe, owner and editor of the English Chronicle, in Bath in 1788. The marriage was childless and, to amuse herself, she began to write fiction, which her husband encouraged.
She published The Castles of Athlin and Dunbayne in 1789. It set the tone for the majority of her work, which tended to involve innocent, but heroic young women who find themselves in gloomy, mysterious castles ruled by even more mysterious barons with dark pasts.
Her works were extremely popular among the upper class and the growing middle class, especially among young women. Her works included A Sicilian Romance (1790), The Romance of the Forest (1791), The Mysteries of Udolpho (1794), and The Italian (1796). She published a travelogue, A Journey Through Holland and the Western Frontier of Germany in 1795.
The success of The Romance of the Forest established Radcliffe as the leading exponent of the historical Gothic romance. Her later novels met with even greater attention, and produced many imitators, and famously, Jane Austen's burlesque of The Mysteries of Udolpho in Northanger Abbey, as well as influencing the works of Sir Walter Scott.
Stylistically, Radcliffe was noted for her vivid descriptions of exotic and sinister locales, though in reality the author had rarely or never visited the actual locations. Shy by nature, she did not encourage her fame and abandoned literature as a pursuit.
She died on February 7, 1823 from respiratory problems probably caused by pneumonia. She was buried in Saint George's Church, Hanover Square in London.