Karo went with his parents, after a brief move to Morocco, to Nikopolis, then a city under Ottoman rule. In Nikopol, he received his first instruction from his father, who was himself an eminent Talmudist. He married, first, Isaac Saba's daughter, and, after her death, the daughter of Hayyim Albalag, both of these men being well-known Talmudists.