The area around the towns of Mikulov, Znojmo, Velké Pavlovice, Bzenec, Strážnice, Kyjov along with the Slovácko region provide 94% of the Czech Republic's vineyards.

The share of inhabitants living in towns and cities on the total population of the region has been steadily decreasing due to suburbanization.

The point with the lowest elevation (150 m) is situated in Břeclav District at the meeting of the rivers Morava and Dyje.

The northern and north-western part of the region is covered by the Bohemian-Moravian Highlands (Czech: Českomoravská vrchovina) and the Moravian Karst.

The Bohemian-Moravian Highlands and the Carpathian Mountains are separated by the Lower-Moravian Valley (Czech: Dolnomoravský úval).

The southern part of the region is predominantly flat and dominated by fields, meadows, and the remainders of riparian forests.

On the evening of 24 June 2021, a large IF4 tornado,[10] the most powerful in modern Czech history,[11] devastated multiple villages within the Břeclav and Hodonín districts.

In Hodonín, a large and multi-story building found at the northern edge of the town had Its roof and interior significantly damaged.

Wooden and steel beams from the roof were found impaled into the ground around the buildings and bent by the wind.

In Mikulčice, A bus with several passengers inside was thrown over a small hill, impacting a one-storey brick home.

Several heavy trailers and tractors as well as large concrete blocks from a hay storing structure were lifted and thrown by the tornado.

[17] The nominal gross domestic product of the South Moravian Region was 671.259 billion CZK in 2021, which is nearly 11% of the national GDP.

The GDP per capita was 562.278 CZK (23.428 EUR) in the same period, which is 98.5% of the national average and the second highest result after region Prague.

Important activities are the meat processing, canning of fruits and vegetables (Znojmia, Fruta), sugar industry, brewing (Starobrno, Černá Hora, Vyškov and Hostan) and winemaking (Lahofer, Znovín Znojmo, Vinium Velké Pavlovice).

Chemical and pharmaceutical industry is concentrated especially in Brno (Pliva-Lachema), Ivanovice na Hané (Bioveta) and Veverská Bítýška (Hartmann Rico).

The South Moravian Region spent 856 million euros, 3.2% of its GDP on science and research in 2022, the highest share of the Czech Republic.