He practiced medicine before getting a licence, but enrolled later at the University of Glasgow and received his M.D. degree in 1745. After training in obstetrics in London and Paris, he opened a practice in London and began teaching. He invented a "machine", an obstetrical manikin, for instructions. Smellie described the mechanism of labor, designed obstetrical forceps, devised a maneuver to deliver the head of a breech, and published his teachings. He is believed to have painted his own portrait.
The William Smellie Memorial Hospital which provided maternity services in Lanark closed in the early 1990s and was re-located to a unit at the Law Hospital in Carluke. This was also closed recently and maternity services moved to Wishaw General Hospital.