He helped suppress the Peasants' War, embraced Protestantism in 1524, tried to reconcile Martin Luther and Ulrich Zwingli and signed the Lutheran Augsburg Confession. He formed the Schmalkaldic League with Johann Friedrich I of Saxony.
He fought to uphold Protestantism against the Catholic Holy Roman Emperor Charles V, Holy Roman Emperor.
He founded the first Protestant university, the University of Marburg, in 1527.
On his death his territories were divided (Hesse becoming Hesse-Kassel, Hesse-Marburg, Hesse-Rheinfels, and Hesse-Darmstadt) between his four sons by his first wife, Catherine of Saxony (daughter of George, Duke of Saxony), namely Wilhelm IV von Hessen-Kassel, Ludwig IV (III) von Hessen-Marburg, Philipp II von Hessen-Rheinfels, and Georg I von Hessen-Darmstadt.