Apprenticed to a stocking weaver, Dodsley ran away and went into domestic service as a footman; during this period he published a poem, Servitude (1729), which was later reissued as The Muse in Livery: or, the Footman's Miscellany (1732). His other early works included a satirical farce, The Toy-Shop (1735). Financed by his friends, who included Alexander Pope, he established himself as a publisher in 1735, publishing Johnson's poem London (1738) and suggesting and backing his Dictionary of the English Language.

Dodsley founded several literary periodicals, including The Annual Register (1758), edited by the political philosopher Edmund Burke. Dodsley himself edited two major collections: A Select Collection of Old English Plays (1744) and A Collection of Poems. By Several Hands (1748). In 1758 his tragedy Cleone began a long run at London's Covent Garden (2,000 copies of its text sold on the day of publication); and in 1759 he retired, leaving the conduct of his business to his brother James.