Born as a member of the House of Hohenzollern, he was the son of Joachim II Hector, Elector of Brandenburg, and his first wife Princess Magdalena of Saxony.

Faced with large debts of 2.5 million guilder accumulated during the reign of his father, John George instituted a grain tax which drove part of the peasantry into dependence on a nobility that was exempt from taxation.

Though a staunch Lutheran opposed to the rise of Calvinism, he permitted the admission of Calvinist refugees from the wars in the Spanish Netherlands and France.

On 13 July 1574, he founded the Berlinisches Gymnasium zum Grauen Kloster, the first humanistic educational institution in Berlin.

In 1577 the Brandenburg electors became co-regent with Duke Albert Frederick of Prussia.