After the Defenestration of Prague, the new government formed of Protestant nobility and gentry gave Ernst von Mansfeld the command over all of its forces. Meanwhile, Catholic nobles and priests started fleeing the country. Some of the monasteries as well as unfortified manors were evacuated and the Catholic refugees headed for the city of Pilsen, where they thought that a successful defence could be organised. The city was well-prepared for a lengthy siege, but the defences were undermanned and the defenders lacked enough gunpowder for their artillery. Mansfeld decided to capture the city before the Catholics were able to gain support from the outside.

On 19 September 1618 Mansfeld's army reached the outskirts of the city. The defenders blocked two city gates and the third one was reinforced with additional guards. The Protestant army was too weak to start an all-out assault on the castle, so Mansfeld decided to take the city by hunger. On 2 October the Protestant artillery arrived, but the calibre and number of the cannons was small and the bombardment of the city walls brought little effect. The siege continued, with the Protestants receiving new supplies and recruits on a daily basis, while the defenders lacked food and munitions. Also, the main city well was destroyed and the stores of potable water soon depleted. Finally, on 21 November, cracks were made in the walls and the Protestant soldiers poured into the city. After several hours of close hand-to-hand combat, all of the town was in Mansfeld's hands. The Battle of Pilsen was the first major battle of the Thirty Years' War.