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Biodiversity is the result of historical and recurrent events acting on populations and species. The Drosophila buzzatii species cluster is distributed along a diagonal of open areas in South America. Combining genetic analyses with species distribution models we evaluated the influence of climatic changes in the demography history of this cluster. We performed a Bayesian Skyline analysis and reconstructed the ancestral areas based on mitochondrial cytochrome oxidase I (mtCOI) gene. We modeled the current distribution and projected it to past (mid-Holocene and Last Glacial Maximum) and future. Our results demonstrate that climate change plays a critical role in historical demography and in defining the current and future geographic ranges of these species. The inter-Andean dry valleys and the Chiquitano Seasonally Dry Tropical Forests (SDTF) in Bolivia are considered the ancestral area for the D. buzzatii cluster. From this area, the migration route was through a west-east corridor from central Andes, throughout Bolivia, Paraguay and Argentina toward eastern and northeastern Brazil, along the edges of rain forest. The responses of the species to the climatic changes differ from the dominant assumptions of expansion during dry/cold weather and contraction during wet/warm weather that characterized the glacial cycles. We suggest that the influence of ecology and the potential responsiveness of each taxon to the environmental dynamics should be considered as well. Predictions for the future suggest a decline of suitable areas for the cluster, threatening biodiversity of these habitats. This work showed the importance of an integrative analysis of genetics and geography information to improve the inferences about demographic history hypotheses for the cluster.