In the mid-14th century, upon the death of Bolesław Jerzy II of Mazovia, king Casimir III of Poland initiated campaigns (1340–1366) to take Galicia-Volhynia. Meanwhile, the heartland of Rus’, including Kyiv, became the territory of the Grand Duchy of Lithuania, ruled by Gediminas and his successors, after the Battle on the Irpen’ River. Following the 1386 Union of Krewo, a dynastic union between Poland and Lithuania, much of what became northern Ukraine was ruled by the increasingly Slavicised local Lithuanian nobles as part of the Grand Duchy of Lithuania. By 1392 the so-called Galicia–Volhynia Wars ended. Polish colonizers of depopulated lands in northern and central Ukraine founded or re-founded many towns.
In the Black sea cities of modern-day Ukraine, the Republic of Genoa founded numerous colonies, from the mid-13th century to the late 15th century, including the cities of Bilhorod-Dnistrovskyi (“Moncastro”) and Kiliya (“Licostomo”), the colonies used to be large commercial centers in the region, and were headed by a consul (a representative of the Republic).
In 1569 the Union of Lublin established the Polish–Lithuanian Commonwealth, and much Ukrainian territory was transferred from Lithuania to the Crown of the Kingdom of Poland, becoming Polish territory de jure. Under the demographic, cultural and political pressure of Polonisation, which began in the late 14th century, many landed gentry of Polish Ruthenia (another name for the land of Rus) converted to Catholicism and became indistinguishable from the Polish nobility. Deprived of native protectors among Rus nobility, the commoners (peasants and townspeople) began turning for protection to the emerging Zaporozhian Cossacks, who by the 17th century became devoutly Orthodox. The Cossacks did not shy from taking up arms against those they perceived as enemies, including the Polish state and its local representatives.
Formed from Golden Horde territory conquered after the Mongol invasion the Crimean Khanate was one of the strongest powers in Eastern Europe until the 18th century; in 1571 it even captured and devastated Moscow. The borderlands suffered annual Tatar invasions. From the beginning of the 16th century until the end of the 17th century, Crimean Tatar slave raiding bands exported about two million slaves from Russia and Ukraine. According to Orest Subtelny, “from 1450 to 1586, eighty-six Tatar raids were recorded, and from 1600 to 1647, seventy.” In 1688, Tatars captured a record number of 60,000 Ukrainians. The Tatar raids took a heavy toll, discouraging settlement in more southerly regions where the soil was better and the growing season was longer. The last remnant of the Crimean Khanate was finally conquered by the Russian Empire in 1783.