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Wyman was born in Weymouth, Massachusetts, the son of Ruth (Sword) and Hollis Judson Wyman, a teacher. His grandparents were Protestant ministers. Wyman earned an A.B. in history from Boston University and a Ph.D. in history from Harvard University. From 1966 until his retirement in 1991, Wyman taught in the History Department at the University of Massachusetts Amherst, where he also chaired the Judaic studies program. Wyman held honorary doctoral degrees from Hebrew Union College and Yeshiva University, both in New York City. He was chairman of the David S. Wyman Institute for Holocaust Studies in Washington, D.C.
Deborah Lipstadt characterizes Wyman's book, Paper Walls: America and the Refugee Crisis, as having stood for many years as "one of the most important books," on American immigration policy in the Nazi years. In Paper Walls Wyman discusses the combination of antisemitism, nativistic nationalism, economic crisis and isolationism that made rescue inconceivable.
In his later work, Wyman's position shifted. He came to believe that the attitude of American Jews during the Nazi era was to be faulted, and that the approach of the Bergson Group was the correct one. If American Jews had taken a more forceful approach, government policy could have been changed.
- Paper Walls: America and the Refugee Crisis, 1938-1941 (University of Massachusetts Press, 1968) ISBN 0-87023-040-9
- The Abandonment of the Jews: America and the Holocaust, 1941-1945 (Pantheon Books, 1984) ISBN 978-0-394-42813-0
- America and the Holocaust (thirteen volumes of the documents used in The Abandonment of the Jews (Garland, 1990)
- The World Reacts to the Holocaust (Johns Hopkins University Press, 1996) ISBN 0-8018-4969-1
- A Race Against Death: Peter Bergson, America, and the Holocaust, with Rafael Medoff (The New Press, 2002) ISBN 978-1-56584-761-3
- "Wyman, David S. 1929- - Dictionary definition of Wyman, David S. 1929- - Encyclopedia.com: FREE online dictionary".
- "About David S. Wyman". 19 January 2017.
- About David S. Wyman The David S. Wyman Institute for Holocaust Studies
- About the Wyman Institute The David S. Wyman Institute for Holocaust Studies
- America and the Holocaust, by Deborah E. Lipstadt, Modern Judaism, Vol. 10, No. 3, Review of Developments in Modern Jewish Studies, Part 1 (Oct., 1990), pp. 283-296