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He studied at the University of Oxford, earning his doctorate at St Antony's College. He subsequently taught at the University of Warwick and various universities in Spain. In 1970, he was elected a Fellow of the Royal Historical Society. In 1984 he was appointed Herbert F. Johnson Professor at the Institute for Research in the Humanities, University of Wisconsin - Madison. He was a Professor of the Higher Council for Scientific Research (CSIC) in Barcelona from 1993 until his retirement in 2002. Since then he has continued lecturing and writing, and lives currently in Spain and in the United States. He is an influential contributor to the pages of the Spanish daily newspaper El Mundo. He considers the most stimulating points of his career to have been when he was received by Pope John Paul II during a private conference in the Vatican, and when Queen Sofia of Spain slipped into one of his classes as a student and took notes during a lecture he was giving at a summer conference in Santander, Spain.
Strongly influenced by the research methods and social philosophy of the historians of the French Annales School, he has attempted to combine quantitative history with sociological analysis and accessible narrative. In reaction against an earlier phase when he became immersed in statistical economic history, he has produced a number of biographies of the rulers of Spain, whom he considers unduly neglected. He has also been one of the leading historians who have attacked the traditional "black legend" view of the Spanish Inquisition. His own views have changed since he published a book about the Inquisition in the 1960s: his 1998 book provides extensive evidence that the Inquisition was not made up of fanatics who rejoiced in torture and executions and that, for example, Inquisition gaols were better run and more humane than ordinary Spanish prisons.
“One of the most important living historians of Spain, Kamen has devoted his career, most famously in his revisionist books on Philip II and on the Spanish Inquisition, to taking on the so-called Black Legend, promoted by Spain’s opponents. That he has in many ways succeeded, thanks to decades of engaged scholarship, in fundamentally altering historians’ understanding of 15th- and 16th-century Spain is testimony to the force of his arguments and the depth and quality of his rigorous, archive-based research.” (The Atlantic Monthly (Boston), 2012).
- The Iron Century: Social Change in Europe, 1550-1660. New York: Praeger Publishers (1972)
- "A Forgotten Insurrection of the Seventeenth Century: The Catalan Peasant Rising of 1688," The Journal of Modern History, Vol. 49, No. 2 (June 1977), pp. 210-30.
- Spain in the Later Seventeenth Century. London: Longman (1980)
- Golden Age Spain. Basingstoke: Macmillan Education (1988)
- European Society 1500-1700. New York; London: Routledge (1984)(1992) [revision of The Iron Century]
- "Lo Statista" in "L'uomo barocco" (R. Villari, ed.) Laterza, Bari, Italy (1991)
- The Phoenix and the Flame. Catalonia and the Counter-Reformation. London and New Haven: Yale University Press (1993)
- Philip of Spain. New Haven: Yale University Press (1997)
- The Spanish Inquisition: A Historical Revision. London and New Haven: Yale University Press (1998) 
- Early Modern European Society. London: Routledge (2000) 
- Philip V of Spain: The King Who Reigned Twice. New Haven: Yale University Press (2001).
- Empire: How Spain Became a World Power, 1492-1763. New York: HarperCollins (2003) 
- The Duke of Alba. London and New Haven: Yale University Press (2004) 
- Spain 1469-1714: a Society of Conflict. London and New York: Longman (2005)
- The Disinherited; Exile and the Making of Spanish Culture, 1492-1975. New York: HarperCollins (2007)
- Imagining Spain. Historical Myth and National Identity. London and New Haven: Yale University Press (2008)
- The Escorial. Art and Power in the Renaissance. London and New Haven: Yale University Press (2010) 
- Henry Kamen, The Spanish Inquisition: A Historical Revision. (Yale University Press, 1998); ISBN 0-300-07880-3 ** Revised edition of his 1965 original.
- On Philip of Spain, by M.N. Carlos Eire in Renaissance Quarterly, vol.52, 1999, "Kamen's Philip is a stunning achievement, not only because of its revisionist outlook and its use of sources, but also because of its style and structure. This is an exemplary piece of scholarship that reads very much like a good novel".
- On Empire, in The Daily Telegraph, "A boldly conceived project that sustains its case with a pugnacious elan that carries the reader through to the final page": 
- On The Disinherited, in The Guardian, "Wonderfully accomplished, beautifully told": 
and in The Weekly Standard, Washington DC, "Henry Kamen is the finest historian of Spain presently writing in any language": 
- On Imagining Spain, Eric Ormsby in The New York Sun, "Drawing on archival sources, unpublished manuscripts, and a vast body of scholarship in several languages, he takes a fresh look at Spanish notions of nationhood, monarchy, and empire. . . . Only someone who loves Spain deeply could have written this book.": 
- On The Escorial: Art and Power in the Renaissance, Prof Patrick Williams, in Literary Review (London), June 2010: "Lively and contentious, informed by a profound understanding of the period, and, as always, elegantly written."