Her first piece, The Chapter of Accidents, a three-act drama based on Denis Diderot's Le père de famille, was produced by George Colman the Elder at the Haymarket Theatre on 5 August 1780 and was an immediate success.

[1] When her father died in 1781, Lee spent the proceeds of the play on establishing a school at Bath, where she made a home for her sisters Anne and Harriet.

[2] Lee also wrote the play Almeyda, Queen of Granada (1796), a long tragedy in blank verse, which opened at Drury Lane on 20 April 1796 but ran for only five nights.

It was so popular that a spin-off novelette appeared in 1820, Rose Douglas; or, The Court of Elizabeth[4][1] William Hazlitt might consider it "dismal" by comparison with the works of Ann Radcliffe, but its influence both on the Gothic school of the Minerva Press, and on figures like Walter Scott is nonetheless clear.

[5] From this work, Italian writer Carlo Federici wrote the play Il paggio di Leicester (Leicester's Page) and, in turn, that became the source of Elisabetta, regina d'Inghilterra, (Elizabeth, Queen of England) the 1812 opera by Gioachino Rossini, the libretto of which was written by Giovanni Schmidt.