structural:reformatting, stylistic:tone
History

The name Don could stem from the Avestan word dānu- ("river, stream"). According to the Kurgan hypothesis, the Volga-Don river region was the homeland of the Proto-Indo-Europeans around 4,000 BC. The Don river functioned as a fertile cradle of civilization where the Neolithic farmer culture of the Near East fused with the hunter-gatherer culture of Siberian groups, resulting in the nomadic pastoralism of the Proto-Indo-Europeans. The east Slavic tribe of the Antes inhabited the Don and other areas of Southern and Central Russia. The area around the Don was influenced by the Byzantine Empire because the river was important for traders from Byzantium.

In antiquity, the river was viewed as the border between Europe and Asia by some ancient Greek geographers. In the Book of Jubilees, it is mentioned as being part of the border, beginning with its easternmost point up to its mouth, between the allotments of the sons of Noah, that of Japheth to the north and that of Shem to the south. During the times of the old Scythians it was known in Greek as the Tanaïs (Τάναϊς) and has been a major trading route ever since. Tanais appears in ancient Greek sources as both the name of the river and of a city on it, situated in the Maeotian marshes. Greeks also called the river Iazartes (Ἰαζάρτης). Pliny gives the Scythian name of the Tanais as Silys.

According to an anonymous Greek source, which historically (but not certainly) has been attributed to Plutarch, the Don was home to the legendary Amazons of Greek mythology.

The area around the estuary has been speculated to be the source of the Black Death in the mid-14th century.

While the lower Don was well known to ancient geographers, its middle and upper reaches were not mapped with any accuracy before the gradual conquest of the area by the Tsardom of Russia in the 16th century.

The Don Cossacks, who settled the fertile valley of the river in the 16th and 17th centuries, were named after the river.

The fort of Donkov was founded by the princes of Ryazan in the late 14th century. The fort stood on the left bank of the Don, about 34 kilometres (21 mi) from the modern town of Dankov, until 1568, when it was destroyed by the Crimean Tatars, but was soon restored at a better fortified location. It is shown as Donko in Mercator 's Atlas (1596). Donkov was again relocated in 1618, appearing as Donkagorod in Joan Blaeu 's map of 1645.

Both Blaeu and Mercator follow the 16th-century cartographic tradition of letting the Don originate in a great lake, labeled Resanskoy ozera by Blaeu. Mercator follows Giacomo Gastaldo (1551) in showing a waterway connecting this lake (by Gastaldo labeled Ioanis Lago, by Mercator Odoium lac. Iwanowo et Jeztoro) to Ryazan and the Oka River. Mercator shows Mtsensk (Msczene) as a great city on this waterway, suggesting a system of canals connecting the Don with the Zusha (Schat) and Upa (Uppa) centered on a settlement Odoium, reported as Odoium lacum (Juanow ozero) in the map made by Baron Augustin von Mayerberg, leader of an embassy to the Tsardom of Russia in 1661.

In modern literature, the Don region was featured in the work And Quiet Flows the Don by Mikhail Aleksandrovich Sholokhov, a Nobel-prize winning writer from the stanitsa of Veshenskaya.