The impact of contrasting environments on organisms can result in the establishment of distinct phenotypic traits. Environmentally induced epigenetic mechanisms directly regulate gene expression and potentially lead to long-lasting effects. How phenotypic, epigenetic, and genetic components of wild populations relate to each other is, however, still largely debated. We examined the effect of broad coastline topography (as bay versus open coast) on the morphological, genetic, and epigenetic (i.e., DNA methylation) traits of the brown mussel Perna perna from four natural populations along the south coast of South Africa (between 33.9 S, 25.7 E and 34.2 S, 22.1 E) collected in April 2014. Several morphometric measurements were taken on the mussel body and byssal thread. The epigenetic and genetic structure of P. perna was assessed using the methylation sensitive analysis of polymorphisms technique. Morphological traits differed among populations, but no clear effect of topography on both morphology and genetics was found. Bay and Open Coast sites differed in the patterns of DNA methylation of selected loci, suggesting that topography shaped the epigenetic profile of populations of P. perna. The environmentally induced changes in the DNA methylation of selected loci were neither correlated with the morphological traits analysed, nor explained by the underlying genetic variance among populations. The relationship amongst epigenetics, morphology, and genetics of P. perna populations was shown to be complex and dynamic. Although inconsistent, the topographically linked variability in epigenetic and the phenotypic differences in genetically close populations of mussels highlights the potential role of the local environment in driving mesoscale differences among populations.