The contemporary socio-spatial differentiation of the Czech Republic is the focus of this article. The main aim is (1) to identify spatial clusters of municipalities formed by similar structural and developmental socioeconomic characteristics, and (2) to uncover the basic socioeconomic factors of the spatial differentiation of municipalities. To achieve the proposed aims a unique dataset covering a wide range of social, demographic, and economic variables at the municipal level is used. The principles of spatial autocorrelations (LISA – local indicators of spatial association) are employed. Very distinct connections between the statistical and the spatial variation of different variables were found, which indicates that the absence of a simple connection between the vertical and the horizontal differentiation of society. From a methodological perspective this article’s major contribution is the construction and testing of procedures which can be used to synthesise the results of the LISA analyses. The synthesis uncovers basic spatial patterns of development mirrored in the formation of the growth and decline poles and axes. The results of cluster analyses indicate the spatial stability and inner homogeneity of the growth areas. Conversely, areas in decline are characterised by a very heterogeneous set of variables differing from region to region.