Rabbi Yaakov Beirav, known as the Mahari Beirav, was born around 5234 (1474) in Maqueda, near Toledo, in Castile. He was probably the first to bear the name "Bei-Rav" (house of study), later carried by his descendants. He studied in the yeshiva of Rabbi Yitzchak Aboab, probably in Guadalajara.

After the expulsion from Spain in 1492 he went to North Africa. He later wrote that at eighteen, before he even had a full beard, he had become the halachic authority and rabbi of the five thousand Jewish households of Fez, amid hunger and want. In Tlemcen he preached in the synagogue with Rabbi Yaakov Kino, and in Algiers he had responsa of the Rashbatz copied, which he later handed to his student Rabbi Yosef Karo. By 1513 he sat on the court of the Nagid Rabbi Yitzchak HaKohen Sholal in Cairo. He served as rosh yeshiva in Jerusalem from 1516 to 1519, returned to Egypt, lived in Safed and in Damascus, and settled permanently in Safed in 1535.

In Safed he headed a yeshiva and was the central figure of the city's spiritual life; its greatest scholars studied with him, foremost among them Rabbi Yosef Karo and Rabbi Moshe of Trani (the Mabit). In 5298 (1538) he set out to renew semicha. Twenty-five Safed sages ordained him so that he could ordain others, but the Ralbach, Rabbi Levi ibn Chaviv, rabbi of Jerusalem, opposed the move and a fierce controversy followed. Rabbi Yaakov nevertheless ordained four scholars, among them Rabbi Yosef Karo and the Mabit. The chain of ordination continued until the mid-seventeenth century, though those ordained refrained from ascribing real halachic force to it.

He was the founder of the Beirav family, active in the Land of Israel and in Egypt. Works: responsa (Venice, 1663), novellae on tractate Kiddushin, glosses on Maimonides' Mishneh Torah where the Maggid Mishneh had not commented, a Seder Chalitzah, and explanations of aggadot.

He passed away on 30 Nissan 5301 (1541), according to the most widely cited date, and rests in the old Jewish cemetery of Safed. A synagogue in Safed's old city bears his name.