Waste management in municipalities is a complex process that can produce very different results depending on the specific local characteristics. When considering larger regions, a common way of differentiating among them is the identification of the various levels of urbanization/rurality. In our study we analyze differences in individual parts of South Moravian Region in the Czech Republic with respect to their urbanization level and compare their performance in municipal solid waste management in period of 2009–2020. For determining the level of urbanization/rurality we construct a simple relative measure using available data on municipal size, population density and distance to the central metropolitan area, including also temporal sociodemographic change over the analyzed period. Aggregated results show that while the generation of residual municipal waste remains relatively stable throughout the whole period, levels of separated municipal waste show notable annual growth rate. When adding the factors of rurality and other characteristics into the analysis, notable differences among the individual districts show up. In districts with higher urbanization, more residual and separated waste is being generated per capita, however further characteristics also play a role. Such findings draw attention to the specific factors that can lay behind different development among various regions and represent a valuable knowledge in the process of designing specific targeted measures and policies that are necessary in situations where there is one common target, for instance European Union’s target of waste recycling rate of 65% by 2030, but there is no simple one-size-fits-all solution how to reach it.