Frankenstein tells the story of Victor Frankenstein, a young scientist who creates a sapient creature in an unorthodox scientific experiment. Shelley started writing the story when she was 18, and the first edition was published anonymously in London on 1 January 1818, when she was 20. Her name first appeared in the second edition, which was published in Paris in 1821.

Shelley travelled through Europe in 1815, moving along the river Rhine in Germany, and stopping in Gernsheim, 17 kilometres (11 mi) away from Frankenstein Castle, where, two centuries before, an alchemist had engaged in experiments. She then journeyed to the region of Geneva, Switzerland, where much of the story takes place. Galvanism and occult ideas were topics of conversation for her companions, particularly for her lover and future husband Percy B. Shelley. In 1816 Mary, Percy and Lord Byron had a competition to see who could write the best horror story. After thinking for days, Shelley was inspired to write Frankenstein after imagining a scientist who created life and was horrified by what he had made.

Though Frankenstein is infused with elements of the Gothic novel and the Romantic movement, Brian Aldiss has argued for regarding it as the first true science-fiction story. In contrast to previous stories with fantastical elements resembling those of later science fiction, Aldiss states, the central character "makes a deliberate decision" and "turns to modern experiments in the laboratory" to achieve fantastic results. The novel has had a considerable influence on literature and on popular culture; it has spawned a complete genre of horror stories, films, and plays.

Since the publication of the novel, the name "Frankenstein" has often been used, erroneously, to refer to the monster, rather than to his creator/father.