Agnes was a daughter of Philip I, Landgrave of Hesse, and his first wife, Christine of Saxony.

The marriage between the two was not arranged by their parents but was initiated by Maurice and Agnes themselves, which at the time was highly unusual.

On 26 May 1555, Agnes married her second husband, John Frederick II, Duke of Saxony.

In the choir of the church St. Peter und Paul in Weimar, however, an unknown author states her death was due to poisoning.

The fact that Agnes of Hesse had married into a rival family is consistent with the murder theory: members of the Albertine branch of the House of Wettin may have suspected her of revealing state secrets to the rival Ernestine branch.