The Grand Duchy of Hesse and by Rhine (German: Großherzogtum Hessen und bei Rhein) was a grand duchy in western Germany that existed from 1806 to 1918. The grand duchy originally formed from the Landgraviate of Hesse-Darmstadt in 1806 as the Grand Duchy of Hesse (German: Großherzogtum Hessen). It assumed the name Hesse and by Rhine in 1816 to distinguish itself from the Electorate of Hesse, which had formed from the neighbouring Landgraviate of Hesse-Kassel. Colloquially, the grand duchy continued to be known by its former name of Hesse-Darmstadt.

In 1806, the Landgraviate of Hesse-Darmstadt seceded from the Holy Roman Empire and joined Napoleon's new Confederation of the Rhine. The country was promoted to the status of grand duchy and received considerable new territories, principally the Duchy of Westphalia. After the French defeat in 1815, the grand duchy joined the new German Confederation. Westphalia was taken by Prussia, but Hesse received Rhenish Hesse in return. A constitution was proclaimed in 1820 and a long process of legal reforms was begun, with the aim of unifying the disparate territories under the grand duke's control. The political history of the grand duchy during this period was characterised by conflict between the conservative mediatised houses (Standesherren) and forces supporting political and social liberalisation. During the 1848 revolutions, the government was forced to grant wide-ranging reforms, including the full abolition of serfdom and universal manhood suffrage, but the reactionary government of Reinhard von Dalwigick rolled most of these back over the following decade. In 1866, Hesse entered the Austro-Prussian War on the Austrian side, but received a relatively mild settlement from the Prussian victors. The grand duchy joined the German Empire in 1871. As a small state within the empire, the grand duchy had limits placed on its autonomy, but significant religious, social, and cultural reforms were carried out. During the November Revolution after World War I in 1918, the grand duchy was overthrown and replaced by the People's State of Hesse.

The portion of the grand duchy on the right bank of the Rhine stretched most of the way from the south of the modern state of Hesse to Frankenberg. The portion on the left bank was located in the modern state of Rhineland-Palatinate. In addition to the great floodplains of the Rhine (Hessian Ried), Main, and Wetterau, the grand duchy also contained upland regions like the Vogelsberg, the Hessian Hinterland, and the Odenwald. In the south, the exclaves of the Wimpfen district [de] extended into the Grand Duchy of Baden.

The territory consisted of two separate areas: the province [de] of Upper Hesse in the north and the provinces of Starkenburg and Rhenish Hesse in the south, as well as a number of much smaller exclaves. The northern and southern sections were separated by a narrow stretch of territory, which belonged to Prussia after 1866 and before that to Duchy of Nassau, the Free City of Frankfurt, and the Electorate of Hesse. About 25% of the land area was forested. The two sections had very different characters:

Upper Hesse was the largest of the three provinces by area. Most of this territory was forested uplands of the Vogelsberg and the Hessian Hinterland. Only a small portion was part of the fertile Wetterau, where there were also brown coal deposits. There were many streams and waterways in the area, but none of them were big enough to serve as transport routes. Agriculture brought only low yields, while there was no industry at all. This led to increasing poverty over the course of the 19th century and massive emigration to the established industrial centres in Germany and overseas. While Upper Hesse was also the largest province by population at the start of the 19th century, by the end of the grand duchy in 1918 it had become the smallest. The only significant institution which was based here was the University of Giessen.

Starkenburg and Rhenish Hesse were totally different. They lay almost entirely on the banks of the Rhine (except for the Odenwald, which faced similar structural problems to the Vogelsberg). Intensive agriculture was possible and profitable in many areas of these plains, such as fruit growing on the Bergstraße and viticulture in Rhine-Hesse. There were two large navigable rivers, the Rhine and the Main, which were the most important transportation routes until the development of the railway. Burgeoning industry developed in this region. The three major centres of the grand duchy were located here: the capital at Darmstadt, the largest industrial centre at Offenbach am Main, and Mainz which was the largest city and the most significant centre for trade.

The grand duchy was divided into three provinces:

The neighbouring states were: