Smollett was born at Dalquhurn, now part of Renton, in present-day West Dunbartonshire, Scotland. He was the son of a judge and land-owner, and was educated at the University of Glasgow, qualifying as a surgeon. His career in medicine came second to his literary ambitions, and in 1739 he went to London to seek his fortune as a dramatist. Although unsuccessful, he obtained a commission as a naval surgeon and travelled to Jamaica, where he settled down for several years. On his return, he set up practice in Downing Street and married a wealthy Jamaican heiress, Anne Lascelles, in 1747. His first published work was a poem about the Battle of Culloden, but it was The Adventures of Roderick Random which made his name. It was modelled on Le Sage's Gil Blas, and was published in 1748. Smollett followed it up by finally getting his tragedy, The Regicide, published, though it was never performed. In 1750, Smollett took his MD degree in Aberdeen, and also travelled to France, where he obtained material for his second novel, The Adventures of Peregrine Pickle, another big success. Having lived for a short time in Bath, he returned to London and published The Adventures of Ferdinand Count Fathom in 1753. He was now recognised as a leading literary figure, and associated with the likes of David Garrick, Oliver Goldsmith, Samuel Johnson and Laurence Sterne. In 1756, he became editor of The Literary Review.
Smollett then began what he regarded as his major work, A Complete History of England, which took from 1757 to 1765. During this period he served a short prison sentence for libel, and produced another novel, The Life and Adventures of Sir Launcelot Greaves (1760). Having suffered the loss of a daughter, he went abroad with his wife, and the result was Travels through France and Italy (1766). He also visited Scotland, and this visit helped inspire his last novel, The Expedition of Humphry Clinker, published in the year of his death. He had for some time been ailing, and had sought a cure at Bath and eventually retired to Italy, where he is buried at Leghorn.
There is a monument to his memory beside Renton Primary School, Dunbartonshire, on which there is a Latin inscription composed by Dr. Johnson. The area around the monument was improved in 2002, with an explanatory plaque.