The glacial–interglacial climate cycles of the Pleistocene played a significant role in dramatically altering species distributions across the globe. However, the climate of the Greater Cape Floristic Region is thought to have been decoupled from global fluctuations and the current Mediterranean climate remained relatively buffered during this period. Here we explore the roles of climate stability and the topographic complexity of the region on the range history of an endemic Little Karoo plant, Berkheya cuneata, using ensemble species distribution modelling and multi-locus phylogeography. The species distribution models projected onto downscaled climate simulation of the Last Glacial Maximum demonstrated a considerable range contraction and fragmentation into the western and eastern Little Karoo, separated by the Rooiberg inselberg. This population fragmentation is mirrored in the phylogeographic structuring of both chloroplast and nuclear DNA. These results suggest that sufficient climatic buffering coupled with regionally complex topography ensured the localised population persistence during Pleistocene climate cycles but these features have also promoted population vicariance in this, and likely other, Little Karoo lowland species.