Born in Evanston, Illinois, Frank Waugh McCulloch was the son of two lawyers, both of whom were active in civic and social causes. He attended Williams College, where he received his A.B. degree in 1926, and Harvard University, where he received his LL.B. in 1929. From 1930 to 1935 McCulloch worked by day for the Chicago firm of Sonnenschein, Berkson, Lautmann, Levinson & Morse, and in the evenings he did social settlement work in the Chicago Commons. From 1935 to 1946, he was the Industrial Relations Secretary for the Council for Social Action of the Congregational Christian Churches of America at its Chicago office. In 1940 was appointed director of the James Mullenbach Industrial Institute, a joint project of the Chicago Congregational Union and the Council for Social Action for which he worked until 1946. In addition, McCulloch was active in a great variety of organizations such as the Chicago Chapter of the League For Industrial Democracy, the North American Committee to Aid Spanish Democracy, the Union for Democratic Action, the Executive Committee of Americans for Democratic Action, the Conscientious Objector's Information and Service Bureau, the Chicago Workers Committee on Unemployment, the American Society for Cultural Relations with Russia, and the Mid-West Institute of International Relations.

In 1946 he became director of the Labor Education Division of Roosevelt University, a position he resigned in 1949 in order to become an administrative assistant to U.S. Senator Paul H. Douglas of Illinois. He held this post until President John F. Kennedy appointed him Chairman of the National Labor Relations Board in 1961, and Lyndon B. Johnson reappointed him to a second term. A firm believer in industrial democracy, McCulloch remained in his position at the NLRB for ten years and then joined the law faculty at the University of Virginia. His courses included Labor Law and Labor Law in Action. From 1971 to 1988 he served on the Public Review Board of the United Auto Workers. In 1972 he became a member of the Virginia Commission on Public Employee Rights, serving for four years. In 1974 he was appointed to succeed former Supreme Court Chief Justice Earl Warren on the Committee of Experts of the International Labor Organization, a United Nations agency, where he served until 1985. For ten years, starting in 1977, he was a member of the Albemarle County Industrial Development Authority. He died in 1996.