Goldsmith was born November 10, 1730, in Pallas, Ireland, the son of an Anglican curate. He received a general education at Trinity College, Dublin, and studied medicine at the universities of Edinburgh and Leiden. He subsequently wandered through Europe, supporting himself by playing the flute and by begging. Later, in England, he practiced medicine, taught school, and eventually worked for various publishers, producing literary works to order. As a hack writer, he was the author of translations, books for children, and articles for newspapers and magazines. These anonymous potboilers were characterized by humor, picturesque descriptions, and a graceful style. Among them was a series of letters, supposedly written by a Chinese traveler, describing London, later reprinted as A Citizen of the World (1762). Once Goldsmith's authorship of this successful series became known in London literary circles, he made many influential friends, including Samuel Johnson, the foremost literary figure of the day; Sir Joshua Reynolds, the greatest English painter of the time; and the statesman and orator Edmund Burke. In 1763, Goldsmith became one of the original nine members of the celebrated literary society known as The Club, presided over by Johnson.

In 1764, Goldsmith's philosophic poem The Traveller was published and established him as an important writer. The publication of The Vicar of Wakefield (1766) is believed to have been hastily arranged by Johnson in order to save Goldsmith from going to jail for debt. In 1770, Goldsmith published the poem The Deserted Village, distinguished for its pastoral atmosphere and felicity of phrasing; it marked the transition in English literature from neoclassicism to romanticism. Goldsmith also produced dramatic works at this time. His first play, the comedy The Good Natur'd Man (1768), was a failure, but She Stoops to Conquer (1773) was an immediate success; it remains one of the best-known comedies of the British drama. In addition to original works, Goldsmith continued to write popular books to order, including histories of Rome, Greece, and England and books on natural history, all readable but not noted for accuracy. Near the end of his life, Goldsmith made an ample income but, through extravagance and openhandedness toward needy friends, spent far more than he earned. He died April 4, 1774, in London.

Goldsmith was buried in the churchyard of the Church of Saint Mary (known as The Temple), London; subsequently The Club erected a memorial to him in Westminster Abbey. The inscription, written by Johnson, includes the tribute "Nullum quod tetigit non ornavit" (He touched nothing that he did not adorn).