Rabbi Isaac Klein was born in a village in Czechoslovakia on September 8, 1905. He migrated to the United States in 1920, determined to further his already considerable Judaic education. This brought him eventually to the Isaac Elchanan Yeshiva (now part of Yeshiva University). Meanwhile he completed high school and received his bachelor's degree from the City College of New York. He earned his way through school by teaching part time.

As he was nearing ordination at the Yeshiva he transferred to the Jewish Theological Seminary of America where he was ordained in 1934. Previously, in 1932, he had married Henriette Levin and was blessed by three children: Hannah (Mrs. Paul Katz), Miriam (Mrs. Saul Shapiro), and Rivkah (Mrs. Gerald Berkowitz).

Rabbi Klein's first pulpit was Kodimoh Congregation, Springfield, Massachusetts, where he served until 1953 except for government service. He proved to be an outstanding chaplain and the story of those years is told in one of his many books. In 1950-1951, appointed by President Truman, he directed Jewish religious affairs in the American occupied sector of Germany. During his Springfield years, Rabbi Klein accomplished two outstanding feats. He received a Ph.D. in 1948 from Harvard University under the sponsorship of the late Professor Harry B. Wolfson. Even more difficult, Rabbi Klein was one of only two men in the century-old history of the Seminary to receive full ordination (S'micha).

In 1953 Rabbi Klein accepted the pulpit of Temple Emanuel in Buffalo, New York. In 1968 this synagogue merged with Temple Beth David to become Temple Shaarey Zedek. Rabbi Klein retired in 1972, spending his winters in California where he taught at the University of Judaism, lectured widely and, despite failing health, wrote many books and articles. His magnum opus, A GUIDE TO JEWISH RELIGIOUS PRACTICE, was published posthumously. A towering figure among the Conservative rabbis of his generation, Rabbi Klein leaned toward tradition both in personal practice and his influence on the movement.

Rabbi-Klein died in Los Angeles on January 23, 1979 and was buried in Buffalo, New York.