He was the son of Frederick I Margrave of Brandenburg-Ansbach Hohenzollern and his wife Sophie Jagiello, daughter of Casimir IV and Elisabeth Habsburg.
Georg had a son named Georg Friedrich Margrave of Brandenburg-Ansbach and Duke of Prussia.
Georg became the legal guardian and raised the minor Louis II of Bohemia Jagiello, King of Hungary and Bohemia.
From 1515 to 1527 Georg governed together with his brother Kasimir, then alone. In 1524 he confessed to the Reformation and he urged his brother Albrecht or Albert of Prussia,who was at that time grand master of the Teutonic Knights, to join the Reformation and secularize Prussia as well. Georg signed the Protestation at Speyer in 1529 and the Augsburg Confession in 1530. He urged the Brandenburg elector Joachim II Hohenzollern to confess to the Lutheran teachings.