After a short period of study in Europe, Paton took up positions at Edinburgh Royal Infirmary and later the Royal Hospital for Sick Children. He received a fellowship in 1883 to work in the University of Edinburgh's physiological department with Professor William Rutherford.[4] In 1886 he became a lecturer in physiology at Surgeons' Hall,[4] and in the same year was elected a Fellow of the Royal Society of Edinburgh in 1886. His proposers were William Rutherford, Andrew Douglas Maclagan, Sir William Turner and Peter Guthrie Tait. In 1889, he was appointed Director of the research laboratory of the Royal College of Physicians of Edinburgh and devoted his time increasingly to research and teaching. During this time he taught at the Edinburgh Extramural School of Medicine, giving lectures in physiology at Surgeons' Hall.[4][6]
He was appointed to the Regius Chair of Physiology at the University of Glasgow in 1906, a position he held until his retirement in 1928.[4]
He was elected a Fellow of the Royal Society in 1914, and served as its Vice President from 1918 to 1921.[7] In 1921 he was elected a member of the Aesculapian Club.[8]
His early research in Edinburgh had centred on diabetes, rickets and the physiology of nutrition. In Glasgow he expanded on these, researching the physiology and pathology of the Parathyroid glands. His interest in nutrition continued. In Glasgow at that time deprivation was common and Paton investigated the relationship between poverty, nutrition, and growth.