The only daughter of William Godwin (Godwin, William) and Mary Wollstonecraft (Wollstonecraft, Mary), she met the young poet Percy Bysshe Shelley (Shelley, Percy Bysshe) in 1812 and eloped with him to France in July 1814. The couple were married in 1816, after Shelley's first wife had committed suicide. After her husband's death in 1822, she returned to England and devoted herself to publicizing Shelley's writings and to educating their only surviving child, Percy Florence Shelley. She published her late husband's Posthumous Poems (1824); she also edited his Poetical Works (1839), with long and invaluable notes, and his prose works. Her Journal is a rich source of Shelley biography, and her letters are an indispensable adjunct.

Mary Shelley's best-known book is Frankenstein; or, The Modern Prometheus (1818, revised 1831), a text that is part Gothic novel and part philosophical novel; it is also often considered an early example of science fiction. It narrates the dreadful consequences that arise after a scientist has artificially created a human being. (The man-made monster in this novel inspired a similar creature in numerous American horror films.) She wrote several other novels, including Valperga (1823), The Fortunes of Perkin Warbeck (1830), Lodore (1835), and Falkner (1837); The Last Man (1826), an account of the future destruction of the human race by a plague, is often ranked as her best work. Her travel book History of a Six Weeks' Tour (1817) recounts the continental tour she and Shelley took in 1814 following their elopement and then recounts their summer near Geneva in 1816.

Late 20th-century publications of her casual writings include The Journals of Mary Shelley, 1814–1844 (1987), edited by Paula R. Feldman and Diana Scott-Kilvert, and Selected Letters of Mary Wollstonecraft Shelley (1995), edited by Betty T. Bennett.