Degler taught history at Vassar College for 16 years (1952–1968). In 1968 he joined the Stanford faculty and taught there for the rest of his career, retiring as Emeritus Professor in 1990. In 1986 Degler was elected President of the American Historical Association. He also served as president of the Organization of American Historians and the Southern Historical Association.
In 1972 Degler was awarded the Pulitzer Prize for History for his book Neither Black nor White (1971), a work comparing slavery and race relations in Brazil and the United States. He earlier wrote Out of Our Past (1959), a study of United States history that is currently used in high school and college classrooms and study chambers throughout the United States. Along with Howard Zinn's A People's History of the United States, it presents neglected and conflicting viewpoints, and thus can be used to help give a more complete view of American history.
He has been described as "a scholarly champion of the common man and woman in American history" and as "a founding feminist". He was one of only two male founding members of the National Organization for Women.
In 1973-1974 he was the Harold Vyvyan Harmsworth Professor of American History at Oxford University.