The Afar Triangle in easternmost Africa is one of biogeographically important regions, whose recent biota is virtually unknown. Here we evaluated the level of evolutionary uniqueness of biodiversity of this region in a wide regional and continental biogeographical context, using rodents as a model group. By combining our recent collections with historical records, and based on genetic data and phylogenetic approaches, we specifically tested whether and to what extent the geographical isolation of the Afar Depression is reflected in allopatric diversification of arid-adapted mammals. We documented the presence of 16 rodent species (four are reported for the first time in Ethiopia and one rediscovered there after more than 100 years) and eight additional species are likely present based on literature data. Comparative phylogeographic analysis suggests that the Afar Triangle can be considered as a part of a larger Somalian biogeographical region, but its fauna is genetically distinct, including the presence of narrow Afar endemics. To a lesser extent, there are taxa with evolutionary affinities to the eastern Sahara-Sahelian region and to the southern Arabian Peninsula. Compared to the Ethiopian Highlands, the rodent fauna of Afar is relatively poor. However, similarly to highlands, the evolutionary distinctiveness of mammals in the Afar Triangle is very high and it can be considered a unique centre of endemism. Our first comprehensive summary of Afar rodents significantly fills the gap in the knowledge of the mammalian fauna of arid regions in Ethiopia and the Horn of Africa in general and highlights the significance of the region for nature conservation.