At the age of 14 Constable was apprenticed to an Edinburgh bookseller, Peter Hill; after six years he left to open his own bookstore. He began to publish theological and political pamphlets, and in 1802 Sydney Smith and Francis Jeffrey chose him as publisher of their new Edinburgh Review (Edinburgh Review, The, or The Critical Journal). Constable's sagacity as a publisher matched their brilliance as editors, and the Review quickly made his reputation as an astute and forward-thinking businessman.

From 1805 to 1808 and after 1814 Constable was a publisher of most of Sir Walter Scott's works, but he soon focused his attention on acquisition of the Encyclopædia Britannica. By 1814 he was sole proprietor and set about creating the sixth edition (1820–23). Constable also conceived the six-volume supplement to the fourth, fifth, and sixth editions. In his enthusiasm and liberality with his authors, Constable overextended his resources, and in 1826 Constable and Company went bankrupt.