Ivan IV had been at war for almost a decade by the time he marched on Polotsk. In 1558 he had invaded the lands of the crumbling Livonian Order along the Baltic, and by 1560 the Order had collapsed entirely - its territory carved up among Sweden, Denmark, the Polish-Lithuanian union, and Muscovy. None of this satisfied Ivan. By 1561 he was at war with Lithuania directly, raiding Mstislavl while Lithuanian forces struck back into Livonia. The Polish-Lithuanian commander Mikolaj Radziwill the Red won an important engagement near Nevel, but neither side could land a decisive blow. In autumn 1562, Ivan decided on a campaign that would settle the matter: a full-scale invasion aimed at the great Lithuanian fortress of Polotsk.

The Moscow army gathered from seventeen cities and concentrated at Mozhaisk. The campaign was framed as a kind of crusade to liberate ancient Russian Orthodox cities from Catholic occupation. Period sources gave wildly inflated numbers - up to 360,000 men - but the surviving Polotsk Book records 31,206. With Tatar reinforcements that joined later, modern estimates put the total at roughly 45,000. The Lithuanian garrison numbered between 2,400 and 6,000. King Sigismund II Augustus tried to open negotiations as the Russian column moved into position; he was rebuffed. On 17 December 1562, the army marched. The transition was difficult, with the column stretched thin and forced to protect its baggage train; some Russian troops defected, giving the defenders advance warning that allowed them to prepare.

The Russians invested the city on 31 January 1563. Polotsk was a wealthy industrial center but well fortified, divided into several walled sections with moats, log palisades, and a citadel. Initial plans for an assault across the frozen lake were judged too dangerous. A relief force under Hetman Mikolaj Radziwill the Red - roughly 40,000 men, by his own claim - tried to bluff the Russians into lifting the siege. It failed. Russian and Tatar detachments moved out to meet the Lithuanians, and Radziwill chose not to give battle. On 5 February, Russian streltsy fired the forward tower and briefly took it before being thrown back. The garrison opened negotiations that evening, and over several days they tried to extend the talks while waiting for relief that did not come. Ivan saw the delay for what it was. The bombardment resumed.

When the heavy siege artillery opened up, parts of the city collapsed. Up to 3,000 yards of wall and structure were destroyed in a single day. Dmitry Khvorostinin's troops took the Veliky Posad - the great suburb - in a fire-lit assault that killed many of the Polish garrison. The remaining defenders attempted a sortie, failed, and capitulated on 15 February. Ivan released the Polish soldiers honorably, with weapons and banners; he did this in part to avoid drawing the Polish crown more deeply into the war. Then he ordered the killing of the Catholic clergy. The Orthodox Jewish community of Polotsk - a centuries-old congregation that had refused baptism - was rounded up and drowned in the Dvina according to multiple contemporary accounts. The reliability of the exact numbers has been debated; the broad fact is recorded. The killings were both an act of religious cruelty and a calculated political message about what kind of ruler now held the city.

Mikolaj Radziwill the Black, the Lithuanian chancellor, organized a propaganda campaign across Europe in response. German leaflets multiplied the casualty figures, claiming Muscovites had killed 80,000 inhabitants of a city that could not have held 20,000. The point of the leaflets was less accuracy than warning: Ivan had taken Polotsk and was prepared to do worse. The fortress remained under Russian control for sixteen years, until Stefan Batory's Polish-Lithuanian army recovered it in 1579. By then Ivan was old, half-mad, and had killed his own son in a rage. The Livonian War he had begun would end with Russia having gained nothing - and having spent a generation of men and treasure to lose what it had briefly held. The dead of Polotsk - the priests, the Jewish congregation drowned in the Dvina - became one of the campaigns the Tsar's enemies kept reminding Europe about for centuries.