Genetic diversity is expected to erode in disturbed habitats through strong selection, local extinctions, and recolonization associated with genetic bottlenecks and restricted gene flow. Despite this general prediction and over three decades of population genetics studies, our understanding of the long-term effect of environmental disturbance on local and regional genetic diversity remains limited. We conducted a population genetic survey of the microcrustacean Daphnia across a landscape subject to anthropogenic stressors from a century of industrial mining. At the local scale we found moderate genetic diversity (i.e., low clonal diversity), characteristic of habitat-specific selective sweeps and local extinctions, but high diversity and strong genetic structure at the regional scale despite the shared watershed of many lakes and exceptional dispersal ability of daphniids. Many habitats experienced changes in species assemblages, with the obligate asexual Daphnia pulex lineages—known only to inhabit ponds—dominating disrupted urban lakes. This habitat transition (pond to lake) was likely facilitated by the disruption of ecological barriers maintaining the genomic separation of these young species. Thus, disrupted habitats can exhibit complex and unexpected genetic patterns of local extinctions and recolonizations, followed by habitat transitions, hybridization and potential speciation events that are difficult to predict and should not be underestimated.