The Persian name is believed to possibly be a reference to gold found in bed of the Zarafshan River and its tributaries, which has ushered prosperity to the region from ancient times.

[2] The range extends over 370 kilometres (230 mi) in an east−west direction along the south of Sughd Region in Tajikistan, reaching the highest point of 5,489 metres (18,009 ft) (Chimtarga Peak) in its central part.

South-west of Panjakent the range crosses from Tajikistan into Uzbekistan, where it continues at decreasing elevations (1,500–2,000 metres (4,900–6,600 ft)) along the internal border between Samarkand and Kashkadarya Regions provinces, until it blends into the desert south-west of Samarkand.

The geological formations in the mountains of the upper Zarafshan Valley contain minerals such as coal, iron, gold alum and sulphur.

Prehistoric Siypantosh Rock Paintings are preserved in the Uzbek portion of the range.

In 330 BC, during the Asian Campaign, troops of Alexander the Great reached the Zarafshan Valley.

The Zarafshan, Yaghnob, and Fan Darya valleys were essentially controlled by local authorities (beks).

By 1870, Russian troops occupied both the Zarafshan and the Yaghnob valleys, with the last operation being the Iskanderkul Expedition in the spring of 1870, under the command of the Major General Alexander Abramov.

After 1870, military topographers started to map the mountains, including the Zarafshan Range.

In 1924, Samarkand Oblast was abolished and split between newly established Uzbek Soviet Socialist Republic and Tajik Autonomous Soviet Socialist Republic, corresponding to the contemporary division between Uzbekistan and Tajikistan.