He was born in Ansbach, the third of eight sons of Margrave Frederick the Elder and his wife Sophie Jagiello, daughter of Casimir IV of Poland and Elisabeth of Habsburg. Through his mother, he was related to the royal court in Buda. He entered the service of his uncle, King Vladislaus II of Bohemia and Hungary, living at his court from 1506. The king received him as an adopted son, entrusted him in 1515 with the duchy of Oppeln, and in 1516 made him member of the tutelary government instituted for Hungary, and tutor of his son Louis II of Hungary and Bohemia.
By the further appropriation of the duchy of Jägerndorf, George came into possession of all Upper Silesia. As the owner and mortgagee of these territories he prepared the way for the introduction of the Protestant Reformation, here as well as in his native Franconia. At an earlier time than any other German prince and any other member of the Hohenzollern line, even before his younger brother Albert, the Grand Master of the Teutonic Order, he turned his eyes and heart to the new faith proceeding from Wittenberg.
After the accession of King Louis II, George was aided in his reforming efforts by Queen Maria, a sister of Charles V and Ferdinand I, who was favorably inclined toward the new doctrine. As the adviser of the young king, George firmly advocated the cause of the new gospel against the influences and intrigues of his clerical opponents and successfully prevented their violent measures. His relationship with Duke Frederick II of Liegnitz, Brieg, and Wohlau, and with Duke Charles I of Münsterberg-Oels, who had both admitted the Reformation into their countries, contributed not a little to the expansion of the gospel in his own territories. But it was his own personal influence, energy, and practical spirit that introduced the new doctrine and founded a new evangelical and churchly life. He made efforts to secure preachers of the new gospel from Hungary, Silesia, and Franconia, and tried to introduce the church order of Brandenburg-Nuremberg, which had already found acceptance in the Franconian territories.
George protested against such half-measures and showed his dissatisfaction with the half-hearted resolutions of the state assembly of October 1526. It was only after the death of his brother that as sole ruler he could successfully undertake and carry out reformation in the Franconian territories, with the assistance of councillors such as Johann von Schwarzenberg and through the new resolutions of the state assembly of Ansbach (1528). At the same time George maintained his correspondence with Luther and Philipp Melanchthon, discussing such questions as the evangelization of monasteries, the use of monastic property for evangelical purposes, and especially the foundation of lower schools for the people and of higher schools for the education of talented young men for the service of church and state. He tried to gain, by his continued correspondence with Luther and other reformers such as Urbanus Rhegius, efficient men for the preaching of the gospel and for the organization of the evangelical church. Hand in hand with the Council of Nuremberg he worked for the institution of a church visitation on the model of that of electoral Saxony, from which after repeated revisions and emendations the excellent church order of Brandenburg-Nuremberg of 1533 was developed. After its introduction in his territories in Franconia and Nuremberg, it was also introduced in his dominions in Upper Silesia.
But neither at the Convention of Schwabach nor at that of Schmalkalden did George approve armed resistance against the emperor and his party, even in self-defense. He opposed the emperor energetically at the Diet of Augsburg in 1530, when the emperor demanded the prohibition of evangelical preaching. King Ferdinand made George the most alluring offers of Silesian possessions if he would support the emperor, but he strongly rejected them. Next to the elector of Saxony, he stands foremost among the princes who defended the reformed faith. After the death of his cousin, Joachim I, who was a strict Romanist, he assisted his sons in the introduction of the Reformation in the territories of Brandenburg. He took part in the religious colloquy of Regensburg in 1541 where Elector Joachim II made a last attempt to bridge the differences between the Romanists and evangelicals and with his nephew requested Luther's cooperation. The Diet of Regensburg was the last religious meeting which he attended.