George Frederick reigned in his native Ansbach, Franconia and Jägerndorf, Upper Silesia since 1556 and, after the death of his cousin Albert Alcibiades in 1557, also in Kulmbach. He took over the administration of the Duchy of Prussia in 1577, when the then-reigning Duke Albert Frederick became ill.
He was the last of the older Franconia line of the House of Hohenzollern. Upon his death Ansbach and Kulmbach were inherited by younger princes of the Brandenburg line according to a domestic treaty in Gera from 1598.
George Frederick rebuilt the palace und forteress Plassenburg, which was detroyed after the second margravian war (1552 - 1554), as one of the most impressive residences of the renaissance in the german empire. He also built the fortress Wuelzburg and the old palace in Bayreuth.
During his regnancy between 1557 and 1603 in the Franconian territories of the Hohenzollern (Brandenburg-Ansbach and Brandenburg-Kulmbach) he kept peace, rebuilt cities and Castles, founded several schools and an Univerity.