Greenberg, universally known as Yitz, stepped down as President of Jewish Life Network/Steinhardt Foundation in July 2007. This capped a storied fifty-year career as a leading thinker, activist, and professional in the American Jewish Community. In those decades he served (including overlapping years) eight years in the Rabbinate [ordained by Beth Joseph (Novaredok) Rabbinical Seminary, 1953], twenty years in academia [PhD Harvard University, 1960; thirteen years at Yeshiva University], twenty-three years as a Founding President of the educational organization CLAL, and ten years as Founding President of a new entrepreneurial philanthropic foundation, Jewish Life Network/ Steinhardt Foundation.

In the 1960s in the Rabbinate he built a nationally leading modern Orthodox synagogue/community in Riverdale, New York, created SAR Academy, a leading day school with particular focus on individual development and values integration, was spiritual guide to Yavneh for Orthodox Jewish student activism on campus, and was one of the founders of the Student Struggle for Soviet Jewry, the trailblazer in the American Soviet Jewry Movement.

Greenberg became an influential figure in the Jewish-Christian dialogue, which led to the revision of Christian teachings on Judaism. In joining the dialogue, he went against the Orthodox establishment and beyond the views of his teacher and spiritual mentor, Rabbi Joseph B. Soloveitchik. In the 1970s, Greenberg was founding chairman of the Department of Jewish Studies of City College of the City University, New York and was one of the founders of the Association for Jewish Studies, the professional organization for academic Jewish Studies. Starting from the 1960s, he was a pioneer in Holocaust education, including service as (Executive) Director of the President’s Commission on the Holocaust in 1979–1980, which conceived (and later supervised the creation of) the United States Holocaust Memorial Museum in Washington, D.C. From 1974–1997, he served as Founding President of CLAL: The National Jewish Center for Learning and Leadership which played a leading role in shifting the agenda of Jewish Federations toward priority for Jewish education and identity. CLAL pioneered pluralistic Jewish education for lay leadership and interdenominational religious dialogue and study for Rabbis.

In 1990s and 2000s, together with Michael Steinhardt and his son, JJ Greenberg of blessed memory, he worked on developing the new entrepreneurial philanthropy for Jewish renewal. Among the projects they initiated were Makor, outreach to Jews in their 20s and 30s, through cutting-edge music, the arts and culture; the Partnership for Excellence in Jewish Education (PEJE) to spread and improve day school education; and birthright Israel, a universal gift of an educational trip for Jews ages of 18–26.

Greenberg’s theological writings on post-Shoah theology, on religious pluralism, on reimagining the relationship of Judaism and Christianity have won a wide following among American Jews and non-Jews alike. In his book, Interpreters of Judaism in the Late Twentieth Century, Professor Steven T. Katz wrote, “No Jewish thinker has had a greater impact on the American Jewish community in the last two decades than Irving (Yitz) Greenberg.”