Zerbst is situated in the Anhalt-Wittenberg region, with its town centre located on the river Nuthe about 13 km (8.1 mi) northeast of the Elbe, halfway between Magdeburg and Wittenberg.

With the 1 January 2010 local government reform, the 21 formerly independent communities of the disbanded Verwaltungsgemeinschaft (municipal association) Elbe-Ehle-Nuthe were incorporated into the town.

The chronicles by Prince-Bishop Thietmar of Merseburg recorded the first mention of a town as Zirwisti urbs in 1018,[5] giving an account of the occupation by the Polish duke Bolesław I Chrobry during the German–Polish War with King Henry II in 1007.

In the early 12th century the Ascanian ruler Albert the Bear had the fortress rebuilt, and the adjacent settlement was first fortified with town walls about 1250.

His descendants continued to rule the Principality of Anhalt-Zerbst until in 1396 it was divided between Prince Sigismund I and his brother Albert IV, and the residence was moved to Dessau.

In 1745 Princess Sophie Auguste Friederike of Anhalt-Zerbst married Peter, Crown Prince of Russia, the heir apparent to the Russian throne.