After graduating in 1701 at Bologna with degrees in philosophy and medicine, Morgagni acted as prosector to A.M. Valsalva, whom he assisted in preparing the latter's celebrated De Aure Humana (1704; Anatomy and Diseases of the Ear). Morgagni then succeeded Valsalva in his position as anatomical demonstrator, but after a time he gave up that post and spent several years in Padua, where in 1710 he became professor of medicine. In 1715 he was promoted to the chair of anatomy.

Morgagni's Adversaria Anatomica (1706–19) established his reputation as an accurate anatomist. It was not until 1761, however, that Morgagni published his greatest work, De Sedibus et Causis Morborum per Anatomen Indagatis (The Seats and Causes of Diseases Investigated by Anatomy), which marked him as a founder of morbid anatomy. The work treats the morbid conditions of the entire body and contains records of 640 dissections. Although he was the first to demonstrate the necessity of basing diagnosis, prognosis, and treatment on a comprehensive knowledge of anatomical conditions, Morgagni made no attempt to exalt pathological anatomy into a science disconnected from clinical medicine and remote from practical needs. Indeed, he was a widely respected clinician who maintained an active practice.