He was educated at St. Mary's College in Baltimore and later studied medicine under Dr. John Buckler.
Along with Charles Frick, David Stewart and Elisha W. Theobald he was involved in founding the Maryland Medical Institute in 1847.
He travelled to Europe in 1853 and worked in hospitals in Paris and Vienna and on his return he became a lecturer in experimental physiology at the University of Maryland.
In 1864 he became a professor of anatomy and physiology at the University of Maryland and in 1869 he succeeded Nathan R. Smith as chair of surgery.
[3][4] Johnston wrote mainly on medical topics, including an entry on plastic surgery for Ashhurst's Encyclopedia.