Evolutionary processes related to climatic changes and ecological factors, such as microhabitat affinities and food specialization, can be important contributors to phylogeographic discordance between codistributed and related species. Here, we evaluate the evolutionary histories of two cactophilic and codistributed Drosophila species (Diptera: Drosophilidae) from South America, Drosophila antonietae and Drosophila meridionalis, where they use mainly Cereus hildmaniannus (Cactoideae: Cereeae) as host, using mitochondrial DNA sequences and species distribution modeling. The diversification of both species was estimated during the Pleistocene. For both species, the distribution of suitable areas through the Last Glacial period to the present showed a similar dynamic from Andes Valley through east and through the Paraná-Paraguay river basin to the Atlantic coastline. The current distribution of D. antonietae was influenced by demographic expansion and putative migration route from northwest to south and then to coast, with two genetic incipient groups with bidirectional genetic flow between them. For D. meridionalis, we suggested a migration route from south to north as well as to coast, with three genetic groups deeply structured with no evidence of demographic expansion. Our comparative results showed that the Quaternary paleoclimatic dynamic has had a similar role in both species (displacement of the high suitability areas) with similar routes but in different directions. Additionally, the Araucaria forest represents a putative biogeographic barrier for Drosophila species and also for host C. hildmaniannus. The phylogeographical differences between these species related to geographical distribution, genetic structure, and demographic history could be explained for differences to adaptation and plasticity to explore a new host.