During the 1940s and 1950s, he pursued his studies at the Hebrew University, earning a doctorate in 1960 for his thesis, which focused on pilgrimage practices during the Second Temple period.

Since then, he has been actively engaged in teaching both within and outside the university, alongside his prolific contributions to scholarly literature through over eighty articles and twelve books.

[5] His son, Prof. Ze'ev Safrai, is a historian in the Department for Israel Studies in Bar Ilan University.

In 1993, Yad Ben Zvi published a volume of studies in honor of Shmuel Safrai, titled Jews and Judaism in the Second Temple, Mishna and Talmud Period.

Edited by Isaiah Gafni, Menachem Stern, and Aharon Oppenheimer, the book features contributions from prominent scholars, including David Flusser, Alon Goshen-Gottstein, Daniel Sperber, Uriel Rappaport and others.