Rabbi Chaim Vital Calabrese was born in Safed on 1 Cheshvan 5303 (1542), the son of Rabbi Yosef Calabrese, who had come from southern Italy; the name "Vital" is the Latin translation of his first name, Chaim. He grew up at the height of Safed's glory, when it was a haven for the exiles from Spain. At fourteen he entered the beit midrash of Rabbi Moshe Alshich, whom Rabbi Yosef Karo, having noticed his gifts, asked to take special care of his education. He then studied Kabbalah under Rabbi Moshe Cordovero.

The arrival of the Arizal from Egypt in 1570 was the turning point of his life. He became his foremost disciple: during the two years the Arizal spent in Safed he hardly left his side, and it was to him that the Arizal entrusted the transmission of his teaching. He devoted the rest of his life to writing it down: his writings, collected in Etz Chaim and the "Eight Gates" (Shemonah She'arim), are the main source of Lurianic Kabbalah. He also wrote Shaarei Kedushah, a guide to spiritual ascent.

He lived in Jerusalem and ended his life in Damascus, where he passed away on 30 Nisan 5380 (1620). After his death his writings spread and had an enormous influence throughout the Jewish world.