Archaeologists have found evidence of prehistoric human settlements in the area, dating back to the Paleolithic era. The figurine Venus of Dolní Věstonice found here is the oldest known ceramic article in the world.

In the classical era, from the 3rd century BC Celtic migrations, the Boii and later in the 1st century, Germanic tribes of Marcomanni and Quadi settled there. Their king Maroboduus is the first documented ruler of Bohemia. During the Migration Period around the 5th century, many Germanic tribes moved westwards and southwards out of Central Europe.

Slavic people from the Black Sea-Carpathian region settled in the area (a movement that was also stimulated by the onslaught of peoples from Siberia and Eastern Europe: Huns, Avars, Bulgars and Magyars). In the sixth century they moved westwards into Bohemia, Moravia and some of present day Austria and Germany. During the 7th century, the Frankish merchant Samo, supporting the Slavs fighting their Avar rulers, became the ruler of the first known Slav state in Central Europe. The Moravian principality arose in the 8th century and reached its zenith in the 9th, when it held off the influence of the Franks and won the protection of the Pope.