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.

Upon his death Ansbach and Kulmbach were inherited by younger princes of the Brandenburg line according to the House Treaty of Gera of 1598.

George Frederick rebuilt the palace and fortress of Plassenburg, which had been destroyed in the Second Margrave War (1552–1554).

During his reign 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 a university.