He was the son of Ernest, Elector of Saxony and his wife Elisabeth, daughter of Albert, Duke of Bavaria. He succeeded his father as Elector in 1486.
In 1502, he founded the University of Wittenberg, where Martin Luther and Melanchthon taught.
He was Pope Leo X's candidate for Holy Roman Emperor in 1519, but helped secure the election of Charles V. Frederick secured an exemption from the Edict of Worms for Saxony, and ensured Luther would be heard before the Diet of Worms in 1521.
He protected Luther from the emperor and pope by taking him into custody at Wartburg Castle after the Diet of Worms.
Frederick himself had little personal contact with Luther and remained Roman Catholic.