Since the Middle Ages, the region formed part of the Khazar Khanate, Kievan Rus', Mongol Empire, Golden Horde, Grand Duchy of Lithuania and the Kingdom of Poland.

The territory was part of the Polish–Lithuanian Commonwealth under the House of Vasa until the Russo-Polish War triggered by Khmelnytsky's Treaty of Pereyaslav, 1654, with the Muscovy alliance.

Many of the towns and cities belonged to the Pale of Settlement and had a substantial Jewish population, while the Polish-speaking nobility was mostly Roman Catholic.

Most of the peasantry became Greek Catholic only in the 18th century, and after the Partitions of Poland, largely converted to Orthodoxy long before the disestablishment of the Unia in 1839.

The right-bank Ukraine was subsequently divided into four provinces (guberniyas), each with its own administration: Kiev, Volhynia, Kherson and Podolia.