Mary and Percy eventually move to Italy where Percy drowns during a sailing trip in 1822. Mary is determined to keep the memory of her late husband alive. She publishes several editions of Percy's writings and adds notes and prefaces to them. She also continues writing her own novels, the most famous one being The Last Man (1826). This book deals with human isolation just as her earlier novel Frankenstein did. She writes numerous short stories and contributes biographical and critical studies to the Cabinet Cyclopædia.

Mary spends the last years of her life in the loving company of her son and two good friends. She tries very hard to free herself from the strains put on her by being the daughter and wife of such well-known people. She maintains her liberal opinions but at the same time tries to fit into a more conservative society. She even writes an apologia in her journal, which reveals "the stresses of a life spent trying to measure up to the example, yet to escape the obloquy, of her parents and husband." Mary Wollstonecraft Shelley dies in 1851 at the age of fifty-three.