Bright graduated in medicine from the University of Edinburgh in 1813. After working in hospitals on the Continent and in London, he became an assistant physician at Guy's Hospital, London, in 1820. He became a full physician there in 1824, eventually retiring from his post in 1843 to devote himself to private practice.

Bright excelled at making meticulous clinical observations and correlating them with careful postmortem examinations. The results of his wide-ranging researches first appeared in Reports of Medical Cases (1827), in which he established edema (swelling) and proteinuria (the presence of albumin in the urine) as the primary clinical symptoms of the serious kidney disorder that bears his name. Bright's subsequent papers on renal disease were published in a second volume of reports (1831) and in the first volume of Guy's Hospital Reports of 1836.