Radcliffe was born as Ann Ward in Holborn, London. 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 (1797). 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 7 February 1823 from respiratory problems probably caused by pneumonia. The funeral took place in Saint George's Church, Hanover Square in London.

Paul Féval, père used her as his protagonist in the novel La Ville Vampire (translated as Vampire City).

In the film Becoming Jane, she is portrayed by Helen McCrory, in a scene where she meets Jane Austen and encourages her to embark on a writing career (there is no historical evidence of such a meeting, though as noted Radcliffe's works had clearly influenced Austen's).

In Maria Edgeworth's book Belinda, Lady Delacour remarks on Clarence Hervey's letters, "Here, my love, if you like description...here is a Radcliffean tour along the picturesque coasts of Dorset and Devonshire."

A biography of Radcliffe, by Deborah Rogers, was published in 1996.

• The Castles of Athlin and Dunbayne (1 volume), 1789, gothic novel. ISBN 0-19-282357-4
• A Sicilian Romance (2 vols.) 1790, gothic novel. ISBN 0-19-283666-8
• The Romance of the Forest (3 vols.) 1791, gothic novel. ISBN 0-19-283713-3
• The Mysteries of Udolpho (4 vols.) 1794. ISBN 0-19-282523-2
• The Italian (3 vols.) 1797. ISBN 0-14-043754-1
• Gaston de Blondeville (4 vols.) 1826, reprinted in 2006 by Valancourt Books ISBN 0-9777841-0-X

Influence on later writers

• Jane Austen
• William Makepeace Thackeray
• Sir Walter Scott
• William Wordsworth
• Honoré de Balzac's novel of the supernatural L'Héritière de Birague (1822) follows the tradition of and parodies Radcliffe's style.
• Samuel Taylor Coleridge
• Mary Shelley
• Percy Bysshe Shelley
• John Keats
• Lord Byron
• Edgar Allan Poe's short story "The Oval Portrait" drew from Udolpho and mentions Radcliffe by name (somewhat disparagingly) in the introduction.
• Charlotte Brontë's Jane Eyre (1847)
• Emily Brontë's Wuthering Heights (1847)
• Charles Dickens's Little Dorrit (1855-7)
• Wilkie Collins's The Woman in White (1860)
• Daphne du Maurier's Rebecca (1938)
• Witold Gombrowicz's Possessed, or The Secret of Myslotch: A Gothic Novel (1939)
• Henry James's short story The Turn of the Screw (1898) in which the governess asks whether there was a "secret at Bly - a mystery of Udolpho..."