Later adopting the ode as his favourite poetic form, Akenside was more than willing to consider himself the English Pindar, one of several aspects of his character that was satirized in Tobias Smollett's novel The Adventures of Peregrine Pickle, in which Akenside appears as the physician in scenes set on the European continent.

Akenside attended the University of Edinburgh, intending to become a minister but instead studying medicine. His first poem, “The Virtuoso,” in imitation of the Elizabethan poet Edmund Spenser, appeared in 1737. The Pleasures of Imagination first appeared in three books in 1744. A fourth book was added later, and the whole poem was extensively revised, finally appearing posthumously in The Poems of Mark Akenside, M.D. (1772). Also in 1744 Akenside turned to satire in An Epistle to Curio, occasioned by the political about-face of William Pulteney, who professed Whig sympathies for years but then accepted the earldom of Bath from a Tory ministry. The following year Akenside published Odes on Several Subjects. He had, meanwhile, been unsuccessful in attempts to establish a medical practice either at Northampton or at Hampstead. In 1747, however, a friend established him in practice in a house in Bloomsbury Square, London. His reputation increased, and he was eventually made physician to the queen. Later works include “Hymn to the Naiads” and “To the Evening Star” (both 1746).