Dirca occidentalis is a rare shrub indigenous to only six counties near the San Francisco Bay in California, United States. We used intersimple sequence repeat (ISSR) markers and automated genotyping to probe 29 colonies of D. occidentalis from four geographically disjunct populations (East Bay, North Bay, Salmon Creek, and Peninsula) and used methods of phylogenetics and population genetics to model variation across the species. Results show that the four disjunct populations are genetically isolated and have undergone divergence. Phylogenetic analyses indicate that the East Bay population was the first to diverge, followed by the North Bay, then the Salmon Creek and Peninsula populations. This order of divergence suggests an intriguing natural history for D. occidentalis that is explained by the dynamic geological and climatic history of the Bay Area. Spatial genetic structure detected for the species suggests an interaction of four factors: limited seed dispersal, clonal regeneration, distances traveled by pollinators, and genetic isolation of the four populations. Genetic diversity within the North Bay and Salmon Creek populations is low, indicating poor ecological fitness and risk of decline. ISSRs resolved phylogeographic structure within D. occidentalis, results unattainable with ITS methods, and the integration of tools of phylogenetics and population biology led to an enhanced understanding of this endemic species.