The end of the 15th - the middle of the 16th centuries were marked by a number of military conflicts between the Grand Duchy of Lithuania and the Moscow State for domination in Eastern Europe. The largest of them was the Livonian War, which became one of the most murderous wars in the history of Polotsk.
During the military operations in February 1563 after a two-week siege Polotskwas taken by the troops of the Grand Prince of Moscow Ivan 4 Vasilyevich, commonly known as Ivan the Terrible. Then Polotsk was under the authority of the Moscow state for the next fifteen years. In August 1579, Polotsk became the part of the Polish–Lithuanian Commonwealth (state created on the basis of the federation of the Grand Duchy of Lithuania and the Crown of Poland.) after the storming of the city by troops under the command of Stefan Batory. The restoration of the economic potential of Polotsk took several decades, and the population, according to some researchers, reached pre-war indicators only by the middle of the 17th century.