Aim The study was aimed at testing whether West Africa can be regarded as a distinct biogeographic region based on amphibian assemblages. If so, we asked what were the relationships of these assemblages with those in Central Africa, and whether West African amphibian distributions showed biogeographic substructure. We further investigated what events or processes may explain the observed patterns. Location Sub-Saharan Africa. Methods Presence–absence data of amphibian assemblages derived from field surveys and the literature were statistically analysed using three different multivariate techniques (consensus clustering, Monmonier analysis and nonmetric multidimensional scaling) to emphasize consistent results. Results We showed that West Africa has unique amphibian assemblages, which could be clearly demarcated from Central African assemblages, particularly by the geographic barrier of the Cross River. Further biogeographic subdivisions were detected to the west of this barrier. Habitat, mainly forest, was the best factor explaining our observed pattern. Overall, intra-regional similarity (e.g. within West Africa) was higher than intra-habitat similarity (e.g. within forest) across regions. Main conclusions Our results are compared with previous works and interpreted in the light of the known evolutionary history of West and Central Africa. The observed pattern may be explained by postulated differences in river continuity through time, with West African rivers serving as more or less constant barriers in contrast to those in Central Africa. Our results demonstrate the uniqueness of West African amphibian assemblages, highlighting the need for their conservation as many are under acute anthropogenic pressure.