The Fergana Valley was known to Han Chinese chroniclers as Dayuan (大宛), the source of the 'heavenly horses' that opened Chinese diplomatic and trade relations with the western world in the 2nd century BCE. Chinese emperors sent military expeditions to obtain Fergana horses; those expeditions in turn opened the Silk Road as a functioning trade network.
The valley's oasis cities — Andijan, Namangan, Kokand, Margilan — became major silk-weaving centres in the 8th–9th centuries after the Samarkand paper-mill innovation. Margilan was the capital of the Silk Route atlas-and-adras production; its Yodgorlik factory still uses the exact reeling, dyeing and weaving methods of the medieval period.
In the 18th century Kokand became the seat of the Kokand Khanate — one of the three great Uzbek khanates alongside Bukhara and Khiva. Russia annexed the Khanate in 1876. Under the Soviets the valley was carved up between three republics (Uzbekistan, Tajikistan, Kyrgyzstan) in a border settlement so intricate that seven enclaves and exclaves still complicate travel.