The Landgraviate of Hesse-Darmstadt came into existence in 1567, when George, youngest of the four sons of Landgrave Philip I "the Magnanimous", received the Hessian lands in the former upper County of Katzenelnbogen.

When, in 1604, the childless Landgrave Louis IV of Hesse-Marburg died at Marburg Castle, a succession dispute to his lands, along with the sectarian differences between Calvinist Hesse-Kassel and Lutheran Hesse-Darmstadt, led to a bitter, decades-long rivalry.

Though Hesse-Darmstadt and Hesse-Kassel reached an agreement in 1627, the quarrels rekindled, resulting inter alia in the Siege of Dorsten and culminating in a series of open battles from 1645, when the Kassel Landgravine Amalie Elisabeth besieged Marburg.

Large parts of the disputed Upper Hesse territory, including Marburg, fell to the elder Kassel line, while Hesse-Darmstadt retained Giessen and Biedenkopf.

In 1806, upon the dissolution of the Holy Roman Empire and the dispossession of his cousin, Elector William I of Hesse-Kassel, Landgrave Louis X joined the Napoleonic Confederation of the Rhine and took the title of Grand Duke of Hesse.