Henry Lee Smith was born in Morristown, New Jersey on July 11, 1913. He received an A.B. (1935), M.A. (1937), and Ph.D. (1938) from Princeton University, and an honorary degree, Litt.D. from Wagner College. Early in his academic career, Smith lectured in English at Barnard College, Columbia University (1938-1940) and Brown University (1940-1942).

In 1935, Henry Lee Smith received a commission as 2nd Lieutenant in the Reserve Officer's Training Corps at Princeton University, and from 1942 to 1946, Smith was a major in the United States Army and served as Officer in Charge, Language Section, Information and Education Division, Army Service Forces. Prior to the war there were no foreign language materials for the bulk of the military and civilian personnel and Smith, along with linguists he recruited, produced language guides, phrase books and military and general purpose dictionaries in many different languages. Under Smiths' direction the linguists also developed what came to be known as the Army method of language instruction, emphasizing the use of phonograph records on which a native speaker recited the foreign words and allowed a pause for repetition by the student.

In 1945, Smith transferred to the Office of the Provost Marshal General and was assigned to duty at Ft. Getty, Rhode Island, and the at Ft. Eustis, Virginia, where he was responsible for selecting German prisoners of war for instruction in English and orientation in democratic principles. In 1946 Smith joined the U.S. Department of State, Washington, D.C., as assistant chief, Division of Training Services, later becoming assistant director of the Foreign Service Institute and continuing in that capacity until 1956.

Henry Lee Smith was a cofounder (1946) of the School of Language and Linguistics, Foreign Service Institute (later the School of Language Studies), under U.S. Department of State and served until 1956 as the school's first director. He was also associated with the institute's School of Languages as a professor of linguistics (1951-1956) and as dean (1955-1956). While with the Foreign Service Institute, Smith again utilized the Army method of language instruction, usually with a native speaker, to instruct Foreign Service officers and clerical personnel before overseas assignments.

Smith returned to teaching in 1956 as professor of linguistics and English at the University of Buffalo, and continued in that capacity until his death in 1972. Smith was the first chairman of the university's new Department of Anthropology and Linguistics (later Department of Anthropology) serving in that capacity until 1965. Smith was also acting director, Program in Linguistics, State University of New York at Buffalo from 1967 to 1968. In 1970 Smith participated in a postdoctoral fellowship at the University of Edinburgh.

At the time of his death (December 13, 1972), Smith was engaged in research in historical linguistics and semology, the relationship of syntactic patterns to meaning.