Natural patchiness and human fragmentation result in habitats that are not continuously distributed. How spatial configuration of patches in fragmented habitats influences biodiversity remains largely controversial. Here, we propose a framework to extend the species–area relationship (SAR) approach to analyze how changes in habitat configuration affect species richness in fragmented habitats. We use hypothetical communities that are characterized by (1) their tolerance to human activities, (2) the dispersal capability of the individuals of any species, (3) the SAR, and (4) the species turnover among patches. Further, the species turnover is a function of (4a) the predictability of species survival and (4b) the species recolonization odds. In our framework, we identify three extreme communities that encompass the richness of all potential different communities, and thus encapsulate the richness of real communities. We propose a graph to visualize the effect of different patch sizes on species richness, an index to quantify those changes, and a second graph using the index to visualize the effect of distance between patches on species richness. After applying our framework and tools to the Tropical Andes, we found strong differences in the impact of natural vs. human-driven fragmentation on richness between biomes. When projecting future richness values under climate change scenarios, the largest sources of uncertainty in our richness calculation (>90%) were species turnover among patches and species dispersal for most of the biomes rather than future climate or species tolerance to human activities. Habitat loss consistently decreased the species richness; however, fragmentation per se often increased it. The increment was mostly linked to the species turnover rate among patches. Our framework is a new theoretical tool to study the main patterns that underlie regional richness and therefore can provide new insights to face spatial habitat reconfiguration caused by human activities.