The present study clarified the taxonomy, phylogeny and historical demography of semicommensal Nile rats (Arvicanthis) from the Nile Valley in Sudan. Nile rats are important crop pests and zoonotic disease reservoirs and are closely associated with agricultural settlements in the Nile Valley. Phylogenetic analysis of the complete cytochrome b gene (1140 bp) of 23 individuals from six localities in Sudan (from two previously recognized species, Arvicanthis niloticus and Arvicanthis testicularis), supported the existence of only a single species, A. niloticus, from the Nile Valley. Historical demography of the Sudanese Nile Valley population inferred from mismatch coefficients indicated that an exponential population expansion event occurred approximately 144 000–288 000 years ago, corresponding in time with early human expansion and colonization from Africa to the Middle East, Europe, and the world. The inferred high level of gene flow and large size of Sudanese Nile populations of A. niloticus is consistent with historically recent (300 years ago) exponential human population growth and intense agricultural activity inferred from archaeological and historical evidence. Two African Arvicanthis clades were well supported by the broader phylogenetic analysis: (1) A. niloticus, Arvicanthis abyssinicus and Arvicanthis neumanni and (2) Arvicanthis rufinus and Arvicanthis ansorgei from western Africa. Within the first clade, divergence between lineages of A. niloticus s.s. from west and north-east Africa (8.9%) suggests specific recognition, but sampling of geographically intermediate localities is required. Based on hypothesized palaeodrainage and palaeoclimatic patterns, we propose a simple model for speciation of Arvicanthis in Africa.