Henry Nash Smith was born on September 29, 1906 in Dallas, Texas. He received a B.A. from Southern Methodist University in 1926 and an M.A. from Harvard in 1929. In 1940, Harvard awarded him a Ph.D. in American Studies.

Nash married Elinor Lucas on April 10, 1936. They had three children, Lloyd Mayne, Janet Carol and Harriet Elinor. His career centered around college teaching, and he held posts at Southern Methodist University, the University of Texas at Austin, the University of Minnesota at Minneapolis, and the University of California at Berkeley, where he was accorded the status of professor emeritus in 1974.

Virgin Land received the John H. Dunning Prize from the American Historical Society in 1951, as well as the Bancroft Prize from Columbia University the same year. In 1960, Smith received an award for distinguished scholarship in the humanities form the American Council of Learned Societies.

Smith's published work included Virgin Land in 1950, Mark Twain, The Development of a Writer in 1962, Mark Twain's Fable of Progress in 1964, and Democracy and the Novel; Popular Resistance to Classic American Writers in 1978. He edited several collections of essays and letters on Mark Twain, and Popular Culture and Industrialism, 1865-1890.

Henry Nash Smith died following a car accident on June 6, 1986, at the age of seventy-nine.