Twersky was born in Boston in 1930, and attended Boston Latin School^[1] and Hebrew College, which was then known as Hebrew Teachers' College. Much of his Torah knowledge was acquired through private study under the tutelage of his father Meshullam Zushe Twersky (his predecessor as the Talner Rebbe of Boston) and his future father-in-law Joseph B. Soloveitchik, rather than through formal yeshiva instruction (Hacker 2005). He then graduated from Harvard in 1952, where he majored in history. In 1949, he spent a year at the Hebrew University of Jerusalem.

Upon his graduation from Harvard, he began studies toward a doctorate in Near Eastern Languages and Civilizations, under the guidance of the scholar of medieval philosophy, Harry Austryn Wolfson. The subject of his doctorate was the twelfth century Provençal Talmudist, Abraham ben David of Posquières (Rabad). Published under the title Rabad of Posquières: A Twelfth-Century Talmudist, it was one of the first academic portraits of a Talmudist written at an American university (Septimus 2005).

Twersky succeeded his father Meshullam Zalman Twersky as the Talner Rebbe of Boston for the last twenty years of his life, serving as the spiritual leader of Congregation Beth David, known colloquially as the Talner Beis Medrash ("the Talner study hall"), which was located in a renovated house in the Brighton neighborhood of Boston. Twersky's lectures in the synagogue on Tuesday nights and late Saturday afternoons were known for their erudition and originality, in the tradition of elite religious Torah study, with the vocabulary and worldliness of a Harvard historian. Twersky and his wife Atarah (née Soloveitchik) played a prominent part in the leadership of Maimonides School. Twersky took on the role of spiritual leader for the school in 1993, after the death of Atarah's father Joseph B. Soloveitchik, who had founded the school in 1937. Atarah was the long-time chair of the School Committee, until 2006, nine years after Twersky's death. She died on February 24, 2023.^[2] The Twerskys' elder son Mosheh, a rabbi and lecturer at Yeshivas Toras Moshe, was murdered in the 2014 Jerusalem synagogue attack.^[3] Their other son, Mayer Twersky, holds the Leib Merkin Distinguished Professorial Chair in Talmud and Jewish Philosophy and is a rosh yeshiva at Yeshiva University and rabbi of the Talner Synagogue of Riverdale. Their daughter Tzipporah Rosenblatt, a lawyer, is married to Jonathan Rosenblatt, rabbi emeritus of the Riverdale Jewish Center in New York City.

Twersky was a pioneer in the introduction of the methodology of the History of ideas, first developed by Arthur O. Lovejoy, into Jewish Intellectual history. He also devoted special emphasis upon the interaction between law and spirituality in the History of Judaism. He founded the Center for Jewish Studies in 1978 and served as its director until 1993.

His research in some respects resembled that of his contemporary and friend Alexander Altmann (Hacker 2005), and his work on Jewish rationalist philosophy brought him into conflict with scholars such as Gershom Scholem and Shlomo Pines, who viewed the medieval rational philosophy typified by Rambam as an alien parasite grafted onto traditional Judaism (Septimus 2005). There has been noted a certain irony in the affection given to this greatest of Jewish rationalists by the descendant of an illustrious Hasidic dynasty (it being the case by and large that Hasidic doctrine has stronger affinity for the mystical over the rational), but Septimus (2005) sees here a coherent and unified search for the spiritual within the rational.

At Harvard, Twersky taught both undergraduate and graduate students. His popular course, Moderation and Extremism, which compared and contrasted the paths to virtue in the works of Aristotle, Maimonides, and Thomas Aquinas, drew over 200 students in 1995, the final year it was taught. Over the course of his thirty years at Harvard, he taught a large number of graduate students. His exacting standards and expectations were legendary. Nevertheless, over thirty individuals completed their doctorates under his guidance. Many of these play leading roles in Jewish studies, both in North America and in Israel. Among these are Edward Breuer (Hebrew University), Bernard Dov Cooperman (University of Maryland), Joseph M. Davis (Gratz College), Lois Dubin (Smith College), David Fishman (Jewish Theological Seminary), Talya Fishman (University of Pennsylvania), Roman A. Foxbrunner, Daniel Frank (Ohio State University), Steven Harvey (Bar Ilan University), Carmi Horowitz (Michlelet Yerushalayim, Jerusalem), Eric Lawee (Bar Ilan University), Diana Lobel (Boston University), David Malkiel (Bar Ilan University), Allan Nadler (Drew University), Ira Robinson (Concordia University), Marc Saperstein (Leo Baeck College, London), Mark (Meir) Sendor, Jacob J. Schacter (Yeshiva University), Bernard Septimus (Harvard University), Marc Shapiro (University of Scranton), Michael Shmidman (Touro University), David Sklare (Machon Ben Zvi), Gregg Stern, Adena Tannenbaum (Ohio State University), Joshua Levisohn, and Jeffrey R. Woolf (Bar Ilan University).

1981: National Jewish Book Award in the Jewish Thought category for Introduction to the Code of Maimonides^[4]

• Hacker, Joseph R. (2005), "Isadore Twersky: Historian of Jewish Culture", in Harris, Jay M. (ed.), Be'erot Yitzhak: Studies in Memory of Isadore Twersky, Cambridge, MA: Harvard University Press, pp. 1–14
• Septimus, Bernard (2005), "Isadore Twersky as a Scholar of Medieval Jewish History", in Harris, Jay M. (ed.), Be'erot Yitzhak: Studies in Memory of Isadore Twersky, Cambridge, MA: Harvard University Press, pp. 15–24

• Carmi Horowitz, Torah and Western Thought: Intellectual Portraits of Orthodoxy and Modernity, Toby Press LLC, 2016.

• Obituary for Isadore Twersky in the Harvard Gazette
• Obituary for Isadore Twersky by Rabbi Hillel Goldberg
• Google Books page for Be'erot Yitzhak: Studies in Memory of Isadore Twersky