The Landgraviate of Hesse-Darmstadt came into existence in 1568, as the portion of George, youngest of the four sons of Landgrave Philipp of Hesse. With the extinction of the Hesse-Marburg and Hesse-Rheinfels lines by 1604, Hesse-Darmstadt, along with Hesse-Kassel, became one of the two Hessian states. While Hesse-Kassel converted to Calvinism and became one of the most zealous exponents of the Protestant cause in the Thirty Years War, Landgrave George II remained a strict Lutheran and maintained a close alliance with Saxony, which resulted in a pro-Habsburg policy after 1635.

Hesse-Darmstadt gained a great deal of territory by the secularizations and mediatizations authorized by the Reichsdeputationshauptschluss of 1803. Most notable was the acquisition of the Duchy of Westphalia, formerly owned by the Archbishop of Cologne, as well as territories from the Archbishop of Mainz and the Bishop of Worms . In 1806, upon the dissolution of the Reich and the dispossession of his cousin, the Elector of Hesse-Kassel, the Landgrave took the title of Grand Duke of Hesse.

At the Congress of Vienna, the Grand Duke was forced to cede Westphalia to Prussia, in exchange for which he received a piece of territory on the Left Bank of the Rhine, including the important federal fortress at Mainz. The Grand Duchy changed its name to the Grand Duchy of Hesse and the Rhine in 1816

In 1867, the northern half of the Grand Duchy became a part of the North German Confederation, while the half of the Grand Duchy south of the Main remained outside. In 1871, it became a constituent state of the German Empire. The last Grand Duke, Ernst Ludwig (a grandson of Queen Victoria and brother to Empress Alexandra of Russia), was forced from his throne at the end of World War I, and the state was renamed the Free State of Hesse.

The majority of the state combined with Frankfurt am Main and the old Prussian province of Hesse-Nassau to form the new state of Hesse following the Second World War. The part of the state on the left bank of the Rhine (Rheinhessen) forms part of the Rheinland-Pfalz state.

Landgraves of Hesse-Darmstadt

• Georg I 1568-1596
• Ludwig V 1596-1626
• Georg II 1626-1661
• Ludwig VI 1661-1678
• Ludwig VII 1678
• Ernst Ludwig 1678-1739
• Ludwig VIII 1739-1768
• Ludwig IX 1768-1790
• Ludwig X 1790-1806 (when he became Grand Duke Ludwig I of Hesse)

Grand Dukes of Hesse (and the Rhine) 1806-1918

• Ludwig I 1806-1830
• Ludwig II 1830-1848
• Ludwig III 1848-1877
• Ludwig IV 1877-1892
• Ernst Ludwig 1892-1918