Lee Seifert Greene was born to Eugene and Margaret (Cline) Green in Esbon, Kansas on May 31, 1905. He was educated at the University of Kansas where he received in B.M. (1927) and his A.B. (1930). He studies at the University of Leipzig as a German-American exchange fellow in 1931, after which he enrolled at the University of Wisconsin. Here, he earned his A.M. degree (1932) and Ph.D. (1934). After graduation, Greene completed his postgraduate work at the Brookings Institution (1934) and the University of Michigan (1935). Greene began his professional career as a Post-Doctoral Fellow at the Social Science Research Council (1937-1938).

In 1936, Greene began working with the Tennessee Valley Authority as a research associate and supervisor of public administration. He came to the University of Tennessee in 1937 where he taught in the Political Science Department until he retired in 1975. In addition to serving as the department's Acting Head (1942-1946) and Head (1946-1971), he also directed the Bureau of Public Administration (1945-1971).

Greene authored a number of books, including Administration of Natural Resources in Tennessee, a history of the University of Tennessee entitled To Foster Knowledge (with James Montgomery and Stanley Folmsbee; 1984), Government in Tennessee (with R,S, Avery, 1962), American Government: Politics and Functions, (1967), Governing the American Democracy, (1980), and Lead Me On: Frank Goad Clement and Tennessee Politics, (1982). He also edited and authored a number of other publications and articles throughout his career. Greene married Dorothy H. Kuersteiner on December 24, 1932 and the couple had two children, Harriet Lee and Robert Everist. Lee S. Greene died on October 18, 1986 and is buried in Mankato, Kansas.