Combe was educated at Eton College. He was left a legacy by a wealthy London merchant, William Alexander, and used it to travel widely and to live in a princely manner. He fell heavily into debt and, after a varied career as private soldier, waiter, teacher, and cook, returned to London about 1771 and thereafter earned his living as a writer. Combe's first Dr. Syntax book (originally published in the Poetical Magazine in 1809) and its successors, The Second Tour of Dr. Syntax in Search of Consolation (1820) and The Third Tour . . . in Search of a Wife (1821), satirize the many 18th- and early 19th-century writers whose “Tours,” “Travels,” and “Journeys” were vehicles for sententious moralizing, uninspired raptures, and sentimental accounts of amorous adventures. The popularity of Combe's work owed much to the illustrations of Thomas Rowlandson (Rowlandson, Thomas). Combe and Rowlandson also collaborated on The English Dance of Death (1815), which contains some of Combe's best verse, and The Dance of Life (1816–17).