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The present-day suburb of Líšeň was a Slav fort, Staré Zámky, at the time of the Great Moravian Empire. Around AD 1000 a settlement was founded on the Svratka river, where the suburb of Staré Brno now stands.

In the 11th century the Přemysl princesses built a castle on Petrov hill. By the middle of the 13th century the town around it had acquired a defensive wall. At this time another castle was built on Špilberk hill. During the reign of John of Luxembourg, Brno became an important centre of arts and trade. In the late 1300s it became Moravia’s capital for the first time. Most of Brno’s monasteries date from that time.

This predominantly Catholic town sided with King Sigismund in the Hussite Wars; the Hussites twice tried to take it but failed. In the mid-15th century Brno sided with an enemy of the Czechs, Matthias Corvinus (Matyáš Korvín). Later in the 16th century Brno turned Protestant and joined the unsuccessful anti-Hapsburg rebellion by the Czech Estates. In the ensuing Thirty Years’ War, the town was able to defend itself against the Swedes from 1643 to 1645.

Botanist Gregor Mendel (1822–84) established the modern science of heredity through his studies of peas and bees at the Augustinian monastery in Brno.

After the Brno–Vienna railway was completed in 1839, Brno developed into a major industrial centre. As the most important town in the Czechoslovak state after Prague, it acquired a university and, in the 1920s, some major exhibition buildings. Brno is one of Europe’s leading venues for trade fairs.