Strayer taught at Princeton University for many decades, starting in the 1930s. He was chair of the history department (1941–1961) and president of the American Historical Association in 1971. Strayer has been credited with training a large percentage of the American medievalist profession; many of his students are still teaching and active. Notable students include Teofilo Ruiz, William Chester Jordan, and Richard W. Kaeuper. Norman F. Cantor often highlighted his status as a student of Strayer's; in spite of anonymous denials by several of Strayer's other pupils of any academic relationship between Cantor and Strayer whatsoever, Cantor names Strayer as his doctoral supervisor in the preface of "Church, Kingship, and Lay Investiture in England".
When not teaching medieval history at Princeton, Strayer was involved with the CIA, as a member of the CIA's Office of National Estimates. The extent of his involvement, at a time when the CIA was running covert operations to destabilize governments around the world (Iran, Brazil, Congo, Dominican Republic, Guyana and Chile), has never been fully assessed or verified.
Norman Cantor recognized three books as most important to Strayer's legacy: Feudalism (1965), which summarized three decades of his research and thinking on the topic; On the Medieval Origins of the Modern State (1970), in which he shows the relevance of medieval historical institutions to modern governmental institutions; and The Reign of Philip the Fair (1980), representing over 30 years of archival research and the most comprehensive work on the topic in any language – other than Jean Favier's Philippe le Bel (1978). Strayer was editor of the Dictionary of the Middle Ages, the largest and most comprehensive encyclopedia on the subject in the English language.