Aim The phylogeographical patterning of taxa distributed in the Cape Floristic Region (CFR) of southern Africa has received much recent attention. Few studies, however, have focused on taxa with broad ecological requirements, such as the South African endemic shrew Myosorex varius (Soricidae). The species is considered a generalist and is distributed throughout the CFR and the grasslands of South Africa. Our aims were: (1) to investigate the fine-scale phylogeographical structure of M. varius through comprehensive spatial sampling across the entire distribution; and (2) to determine if the distribution of genetic structuring was correlated with environmental factors such as seasonal rainfall regimes. Location South Africa. Methods The phylogeographical structure of M. varius was determined by making use of 1029 sequenced characters derived from two independent markers (the mitochondrial hypervariable control region and an intron of a nuclear gene, signal transducer and activator of transcription 5A – STAT). Bayesian analysis of population structure (baps) and spatial genetic landscapes were used to describe broad-scale patterns of genetic diversity across the entire distribution of M. varius. Results Several geographically correlated lineages were detected within the species. The northern lineage comprised all individuals collected from the grassland and savanna habitats of South Africa and, although genetically diverse, did not show any significant geographically correlated substructure. The southern lineage, represented by individuals collected from the Western and Eastern Cape provinces of South Africa, displayed considerably more phylogeographical partitioning, with populations of M. varius in this region subdivided into western and eastern CFR groupings. Main conclusions Contrary to expectations, this study recovered high levels of spatial genetic structuring within the southern African generalist shrew species M. varius. This phylogeographical structure is consistent with that proposed by previous studies on other unrelated taxa, and this study contributes significantly to the growing body of work highlighting the importance of rainfall and associated vegetation types as factors influencing biodiversity patterns in the region.