She also edited and promoted the works of her husband, the Romantic poet and philosopher Percy Bysshe Shelley. Her father was the political philosopher William Godwin and her mother was the philosopher and feminist activist Mary Wollstonecraft.

Shelley's mother died less than a month after giving birth to her. She was raised by her father, who provided her with a rich if informal education, encouraging her to adhere to his own anarchist political theories. When she was four, her father married a neighbour, Mary Jane Clairmont, with whom Shelley came to have a troubled relationship.

In 1814, Shelley began a romance with one of her father's political followers, Percy Bysshe Shelley, who was already married. Together with her stepsister, Claire Clairmont, she and Percy left for France and travelled through Europe. Upon their return to England, Shelley was pregnant with Percy's child. Over the next two years, she and Percy faced ostracism, constant debt and the death of their prematurely born daughter. They married in late 1816, after the suicide of Percy Shelley's first wife, Harriet.

In 1816, the couple and Mary's stepsister famously spent a summer with Lord Byron and John William Polidori near Geneva, Switzerland, where Shelley conceived the idea for her novel Frankenstein. The Shelleys left Britain in 1818 for Italy, where their second and third children died before Shelley gave birth to her last and only surviving child, Percy Florence Shelley. In 1822, her husband drowned when his sailing boat sank during a storm near Viareggio. A year later, Shelley returned to England and from then on devoted herself to the upbringing of her son and a career as a professional author. The last decade of her life was dogged by illness, most likely caused by the brain tumour which killed her at age 53.