Landscape fragmentation is increasingly considered an important environmental indicator in the fields of sustainable land use and biodiversity. To set goals for future development and to plan appropriate measures, suitable empirical data on the degree of landscape fragmentation are needed to identify trends and compare different regions. However, there is still a significant lack of data on landscape fragmentation as an indicator, despite the substantial scientific literature on this topic, likely because of confusion over the definition of "fragmentation," questions associated with scale and data issues, and lack of general agreement on a fragmentation measure. This study presents a state-wide quantitative analysis of landscape fragmentation in Baden-Württemberg, Germany, by means of the "effective mesh size" (meff), which characterizes the anthropogenic penetration of landscapes from a geometric point of view and is based on the probability that two randomly chosen points in a landscape are connected, i.e., not separated by barriers such as roads, railroads, or urban areas. Baden-Württemberg is fragmented to a far greater extent than indicated by previous studies. The meff has decreased by 40% since 1930. This development is strongly related to the growing number of inhabitants, the increased use of motorized vehicles, and the hierarchical regional planning system based on the central place theory. To illustrate the suitability of the meff method for environmental monitoring, as a planning instrument and as an assessment instrument for impact assessment studies, we explored several variations of applying the method with regard to choice of fragmenting elements, consideration of noise bands, spatial differentiation (e.g., administrative districts vs. ecoregions), and way of dealing with patches at the boundaries of the reporting units. Depending on the objectives of the investigation (e.g., recreational quality vs. suitability for wildlife habitat), different variations may be most appropriate. The insights and quantitative results from Baden-Württemberg provide a yardstick for analyzing and assessing landscape fragmentation in other countries.