Born in the northern Italian town of Bertinoro, Rabbi Obadiah studied with some of the most distinguished Italian Jewish scholars, including Rabbi Joseph Colon. In 1486 he moved to the Holy Land, where he was accepted as the acknowledged leader of Jerusalem's heterogeneous Jewish community. For a time, he lived in Hebron.
Rabbi Obadiah's copmmentary is a brief one, compiled largely from earlier works. The principal foundation is Rashi's commentary to the Babylonian Talmud. In many places, especially in those tractates for which there is no Babylonian Talmud (and hence no Rashi) he utilized Maimonides' Mishnah commentary and occasionally that of Rabbi Samson of Sens, and in rare instances he cites his own teachers or his personal interpretations (as when he identifies trees and plants by their Italian names). Following Maimonides' precedent, he indicates which of the views in the Mishnah is the accepted one.