An early Celtic presence in what is now Hesse is indicated by a mid 5th century BC La Tène style burial uncovered at Glauberg. The region was later settled by the Germanic Chatti tribe in ca. the 1st century BC, and the name Hesse is a continuation of that tribal name. In the early Middle Ages, a Frankish gau comprising an area around Fritzlar and Kassel and a Saxon one further north were known as Hessengau. In the 9th Century the Saxon Hessengau also came under the rule of the Franconians. In the 12th century it was passed to Thuringia.

In the War of the Thuringian Succession (1247-64), Hesse gained its independence and became a Landgraviate within the Holy Roman Empire. It shortly rose to primary importance under Landgrave Philip the Magnanimous, who was one of the leaders of German Protestantism. After Philip's death in 1567, the territory was divided up among his four sons from his first marriage (Philip was a bigamist) into four lines: Hesse-Kassel, Hesse-Darmstadt, Hesse-Rheinfels and the also previously existing Hesse-Marburg. As the latter two lines died out quite soon (1583 and 1605, respectively), Hesse-Kassel and Hesse-Darmstadt were the two core states within the Hessian lands. Several collateral lines split off during the centuries, such as in 1622, when Hesse-Homburg split off from Hesse-Darmstadt. In the late 16th century, Kassel adopted Calvinism, while Darmstadt remained Lutheran and subsequently the two lines often found themselves on different sides of a conflict, most notably in the disputes over Hesse-Marburg and in the Thirty Years' War, when Darmstadt fought on the side of the Emperor, while Kassel sided with Sweden and France.

Hesse-Kassel was elevated to the rank of an Electorate in 1803, but this remained without effect as the Holy Roman Empire was disbanded in 1806. The territory was annexed by the Kingdom of Westphalia in 1806, but restored to the Elector in 1813. While other Electors had gained other titles, becoming either Kings or Grand-dukes, the Elector of Hesse-Kassel alone retained the anachronistic dignity. The name survived in the term Kurhessen, denoting the region around Kassel. In 1866 it was annexed by Prussia, together with the Free City of Frankfurt, Hesse-Homburg and the duchy of Nassau, which established the province of Hesse-Nassau.

Hesse-Darmstadt was elevated to the rank of a Grand Duchy in 1806. In the War of 1866, it fought on the side of Austria against Prussia, but retained its autonomy in defeat, because a greater part of the country was situated south of the Main river and Prussia did not dare to expand beyond the Main line as this might have provoked France. But the parts of Hesse-Darmstadt north of the Main river (the region around the town of Gießen, commonly called Oberhessen) were incorporated in the Norddeutscher Bund, a tight federation of German states, established by Prussia in 1867. In 1871 the rest of the Grand Duchy joined the German Empire. Around the turn of the century, Darmstadt was one of the centres of the Jugendstil.

Until 1907, the Grand Duchy of Hesse used only the Hessian red and white lion as its coat-of-arms.

The revolution of 1918 transformed Hesse-Darmstadt from a monarchy to a republic, which officially renamed itself to "Volksstaat Hessen" (People's State of Hesse). The parts of Hesse-Darmstadt on the western banks of the Rhine (province Rheinhessen) were occupied by French troops until 1930 under the terms of the Versailles peace treaty that officially ended WWI in 1919.

After World War II the Hessian territory left of the Rhine was again occupied by France, whereas the rest of the country was part of the US occupation zone. The French separated their part of Hesse from the rest of the country and incorporated it into the newly founded state of Rhineland-Palatinate (Rheinland-Pfalz). The United States, on the other side, proclaimed the state of Groß-Hessen (Greater Hesse) on 19 September 1945, out of Hesse-Darmstadt and most of the former Prussian province of Hesse-Nassau. On December 4, 1946 Groß-Hessen was officially renamed Hessen.

The state is called Hessen in German and Hesse in English; the English name for the state was taken from French. An inhabitant of the state is a Hesse (masculine) or Hessin (feminine) in German and a Hessian in English. Occasionally the German term Hessen is also used in English. Hessia is another variant, although rarely used. Hesse refers to the germanic tribe of the chatts, which used to settle in the region in the first centuries B.C.