He was a titular Duke of Saxony from the Ernestine branch of the House of Wettin.

John Frederick was the fourth and youngest son of Elector of Saxony Johann Frederick the Magnanimous (1503–1554) from his marriage with Sibylle (1512–1554), the daughter of Duke John III, Duke of Cleves.

Because he was a minor, he and his possessions were under the guardianship and regency of his eldest brother John Frederick II until 1557.

However, he concluded a contract with his eldest brother, who would administer the apanage for four years.

John Frederick III died unmarried and childless in 1565, at the age of 27.