Romein began writing while studying humanities at the University of Leiden (1914–1920). Of his professors the historian Johan Huizinga inspired him the most. During his studies and impressed by the First World War and the Russian Revolution he became interested in Marxism. He translated Franz Mehring's biography on Karl Marx into Dutch. After the couple moved to Amsterdam in 1921, he became an editor of the daily De Tribune of the young Communistische Partij Holland (CPH, Communist Party of Holland). In addition, he worked as a freelance writer and translator. Already in 1916-1918 he published a Dutch translation of Romain Rolland's Jean Christophe (10 vols., with an introductory essay). In 1924 he received his doctoral degree, with the highest distinction, at the University of Leiden with the dissertation Dostoyevsky in the Eyes of Western Critics. In 1927 he left the communist party, but he remained interested in Marxism and in the political development of the Soviet Union and of Asia. After publishing a book on the history of the Eastern Roman Empire (Byzantium, 1928) he translated and edited the Harmsworth's Universal History of the World into Dutch, in co-operation with other historians (1929–1932, 9 vols.), with three added chapters written by himself. His first book publication in the field of Dutch history was a pioneering study on the history of Dutch historical writing during the Middle Ages (1932). His most famous books include a history of The Low Countries (1934) and a four-volume work with 36 short biographies of important Dutch (1938–1940), both in cooperation with his wife and fellow historian Annie Romein-Verschoor. In 1939, Romein was appointed professor of history at the University of Amsterdam. He survived World War II after being held hostage as a prisoner for three months by the German police in the notorious Amersfoort police detention camp, and returned to writing and teaching. In 2011 Jan Romein and his wife were posthumously awarded the title "Righteous among the Nations" by Yad Vashem in Jerusalem, for offering a hiding place to a persecuted Jewish fellow-citizen during the German occupation.
In 1937, he published an essay on technology called "The dialectics of progress" (in Dutch: "De dialectiek van de vooruitgang") in which he describes a phenomenon called the "Law of the handicap of a head start" ("Wet van de remmende voorsprong"), as part of the series "The unfinished past" (in Dutch: "Het onvoltooid verleden"). This article was also published in German as "Dialektik des Fortschritts" in: Mass und Wert. Zweimonatsschrift für freie deutsche Kultur (eds. Thomas Mann and Konrad Falke), vol. 2 (Zurich, Switzerland, 1939).
In 1946, Annie Romein received a copy of Anne Frank's diary which she tried to have published. When she was unsuccessful, she gave the diary to her husband, who wrote the first article about the diary and its writer, for the newspaper Het Parool. Interest raised by his article led to the diary being published the following year. Also in 1946, he introduced the theory of history as a subject in the academic curriculum. Soon after the beginning of the Cold War his marxist conceptions, though undogmatic, had placed him in relative isolation, and in 1949 he was denied entry to the United States for an intended speaking engagement at an international scholarly conference in Princeton. Instead, he was welcomed as a guest professor in the young republic of Indonesia during the 1951–1952 academic year. He devoted the latter part of his life to writing a history of Europe during the 25-year period from 1889 to 1914: The Watershed of Two Eras. Europe in 1900, which was published posthumously in 1967 (English edition 1978). It is an attempt at writing "integral history" of the transitional decades from the 19th to the 20th century, during which Europe's supremacy in the world started waning. The book devotes chapters to all aspects of European history during this period: political, economic, social, cultural, scientific, literature, art, emancipation movements etc. Due to a chronic illness, which became manifest in 1959, he limited his professorship at the University of Amsterdam to solely Theoretical History. He died in Amsterdam in 1962.
- Dostojewskij in de Westersche critiek. Een hoofdstuk uit de geschiedenis van den literairen roem [Dostoyevsky in the Eyes of Western Critics. A chapter from the history of literary fame], 1924 (doctoral dissertation, cum laude, University of Leiden).
- Byzantium. Geschiedkundig overzicht van staat en beschaving in het Oost-Romeinsche Rijk [Byzantium. Historical survey of state and civilisation in the Eastern Roman Empire], 1928.
- Geschiedenis van de Noord-Nederlandsche geschiedschrijving in de Middeleeuwen; Bijdrage tot de beschavingsgeschiedenis [History of the Northern-Dutch Historiography during the Middle Ages. A contribution to civilisation history], 1932.
- De Lage Landen bij de zee. Geïllustreerde geschiedenis van het Nederlandse volk van Duinkerken tot Delfzijl [The Low Countries near the sea. An illustrated history of the Dutch people from Dunkirk to Delfzyl], 1934 (8th, rev. & augm. ed. 1979).
- Het onvoltooid verleden [The Unfinished Past. Essays], 1937 (2nd, augm. ed. 1948).
- Erflaters van onze beschaving. Nederlandse gestalten uit zes eeuwen (with Annie Verschoor), 4 vols. [The Testators of our Civilization. Dutch Personages of six centuries], 1938–1940 (13th ed., in one vol., illustr. 1979). Abridged German edition (transl. U. Huber-Noodt): Ahnherren der holländischen Kultur. Vierzehn Lebensbilder mit 13 Porträts, 1946 (2nd ed. 1961).
- De biografie, een inleiding [The Biography; an introduction], 1946 (2nd ed. 1951). German edition (transl. U. Huber-Noodt): Die Biographie; Einführung in ihre Geschichte und ihre Problematik, 1948.
- Theoretische Geschiedenis [Theoretical History], 1946. Eng. ed.: Theoretical History, in: Journal of the History of Ideas, vol. 9, 1948, pp. 53–64.
- Apparaat voor de studie der geschiedenis [Apparatus for the study of history], 1949 (9th rev. ed. 1979).
- In de Hof der Historie. Kleine encyclopaedie der theoretische geschiedenis [In the Garden of History. A small encyclopedia of theoretical history], 1951 (2nd ed. 1963).
- Asia bergolak, setengah abad sedjarah Asia dalam lebih dari 600 gambar 1900 sampai sekarang, oleh J.M. Romein dan W.F. Wertheim; teks-teks penghubung oleh H.M. van Randwijk, dan terdjemahan oleh Amal Hamzah, 1954.
- A World on the Move; a history of colonialism and nationalism in Asia and North Africa from the turn of the century to the Bandung Conference (compiled following an outline of events and dates prepared by J.M. Romein and W.F. Wertheim, who also have written the introductory chapters; captions and running text by H.M. van Randwijk. Transl. from the Dutch by James S. Holmes and A. van Marle), 1956.
- Aera Asia. Terdjadinja, perkembangan dan kemenangan Nasionalisme di Asia dalam abad ke-20. Diselenggarakan bersama-sama dengan J.E. Romein; dan terdjemahan oleh Nur Tugiman (Indonesian translation of The Asian Century), 1958.
- Das Jahrhundert Asiens, Geschichte des modernen asiatischen Nationalismus; in Zusammenarbeit mit J.E. Romein, übersetzt von H. Jolenberg, 1958.
- Over integrale geschiedschrijving [On the writing of Integral History], 1958.
- "The Common Human Pattern; the origin and scope of historical theories", in: Delta, review of arts, life and thought in the Netherlands, Summer 1959, pp. 5–20.
- The Asian Century: A History of Modern Nationalism in Asia (with Jan Erik Romein, transl. by R.T. Clark, with a foreword by K.M. Panikkar), 1962. German edition 1958, Indonesian ed. 1958, Japanese ed. 1961.
- "Change and Continuity in History: The Problem of the 'turnover'," in: Delta, review of arts, life and thought in the Netherlands, Spring 1963, pp. 27–40.
- "The Significance of the Comparative Approach in Asian Historiography. The National and Social Revolution in Asia and the Time Factor", in: An Introduction to Indonesian Historiography. Eds. Soedjatmoko, Mohammed Ali, G.J. Resink, George McT. Kahin, 1965 (3rd ed. 1975), pp. 380–394.
- History of Mankind: Culture and Scientific Development, Volume VI: The Twentieth Century (part of a UNESCO-project). Authors/editors: Caroline F. Ware, K. M. Panikkar, and Jan M. Romein, 1966.
- Op het breukvlak van twee eeuwen [On the Watershed of Two Centuries], 2 vols., 1967 (2nd ed., in one vol., with sub-title: De westerse wereld rond 1900 [The Western World around 1900]. Illustr. 1976). American edition:
- The Watershed of Two Eras. Europe in 1900 (transl. Arnold J. Pomerans. With a biographical and bibliographical introduction by Harry J. Marks, a foreword by Annie Romein-Verschoor, and a preface by Maarten C. Brands), 1978 (first paperback ed. 1982).
- Historische lijnen en patronen. Een keuze uit de essays [Historical headlines and patterns. Selected Essays], 1971 (with a preface by Maarten C. Brands; 2nd ed. 1976).
- Het Parool, April 3, 1946. first published discussion of Anne Frank's diary.
- Jan M. Romein, "The Significance of the Comparative Approach in Asian Historiography. The National and Social Revolution in Asia and the Time Factor", in: An Introduction to Indonesian Historiography. Eds. Soedjatmoko, Mohammed Ali, G.J. Resink, George McT. Kahin (Ithaca, New York: Cornell University Press, 1965), pp. 380-394.
- See: http://www1.yadvashem.org/yv/en/righteous/pdf/righteous_june_2011.pdf
- See: André C. Otto, Het ruisen van de tijd. Over de Theoretische Geschiedenis van Jan Romein [The Rustle of Time: on the Theoretical History of Jan Romein]. Ph.D. dissertation. Book edition published by the International Institute of Social History, Amsterdam 1998 (English summary on pp. 279–283).
- See the book review by Allen R. Douglas, 'Marx and Huizinga: Jan Romein As Historian', in: The Virginia Quarterly Review (VQR, University of Virginia, Charlottesville, VA., Winter 1980), pp. 152–161.