She left her husband, a middle-aged clergyman, for the stage, supporting herself also by writing and adapting works for the theatre. She then turned to the extravagantly passionate fiction for which there was then a vogue, adopting the technique of writing novels based on scandals involving leaders of society, whom she denoted by initials. (The British Museum in London has a key giving their full names.) Among such works are Memoirs of a Certain Island Adjacent to the Kingdom of Utopia (1725) and The Secret History of the Present Intrigues of the Court of Caramania (1727).

Alexander Pope attacked her with coarse brutality in his satirical poem The Dunciad, and Jonathan Swift called her a “stupid, infamous woman.” Pope's attack, which she attempted to counter with The Female Dunciad (1729), caused her to cease writing for almost 16 years. Later, she achieved some success with The Female Spectator (1744–46), the first periodical to be written by a woman, and with her realistic novel The History of Jemmy and Jenny Jessamy (1753).