Born on 1 May 1923 in Elkton, Maryland, James Edward Duffy was one of the forerunners in the systematic study of African history in the United States. His contributions to the development of modern historiography on contemporary Portuguese colonialism were highly significant, as he was among the first to analyse various aspects of the Portuguese colonial system in Africa. His work particularly focused on indigenous politics and race relations between the Portuguese and Africans.

Duffy studied at the University of North Carolina, where he completed his BA in 1944.He briefly worked there as a Spanish tutor. Before 1946, he married Chase Duffy, who, like him, was a graduate of the University of North Carolina. Chase later achieved distinction as an editor, holding positions at the University of North Carolina Press, Harvard University Press, the Philips Academy's Peabody Museum (Andover), and Digital Press. She was also a prominent political activist in the Democratic Party until her death on 16 May 2011.

In 1946, James Duffy moved to Guatemala, where he and his wife worked as English teachers at the Instituto Guatemalteco Americano [Guatemalan American Institute], a cultural centre funded by the US State Department. During his time in Guatemala, he earned an MA in Spanish from the University of San Carlos de Guatemala in 1947. This period also marked the beginning of his friendship with another eminent Africanist, Philip D. Curtin, who later became his doctoral colleague at Harvard (Philip D. Curtin, On the Fringes of History… , 2005, pp. 48, 52-53). His time in Guatemala allowed him to explore and travel extensively across Latin America—a passion for travel that he would revisit years later in Africa, always accompanied by his wife. Back in the United States, after concluding his work with the State Department, James Duffy pursued a doctorate in Portuguese Literature at Harvard University, one of the most prestigious academic institutions in the country. During his doctoral studies, he was mentored by Francis M. Rogers, a leading scholar of Portuguese language and culture in North American academia and the director of the Department of Romance Languages and Literatures at Harvard. Upon completing his doctorate in 1952, Duffy embarked on a career in academia, dedicating most of his professional life to teaching. He served as a professor of Romance Languages, specialising in Spanish, at Brandeis University in Waltham, Massachusetts. Notably, in the late 1950s, Duffy declined an offer from his friend Philip D. Curtin to join the University of Wisconsin, opting to continue teaching at Brandeis instead.

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