Anthropogenic climate change is expected to accelerate environmental changes in the arid and semi-arid zones of southern South America, but its impacts on xerophytic plants in these regions are underexplored. Species distribution modeling allows predicting potential distributions and assessing climate change impacts on biodiversity. In this comparative research, we modeled the geographical distribution of five xerophytic Senna species (series Aphyllae), characteristic of the Chaco, Monte, and Espinal biogeographic provinces, under various future climate scenarios and atmospheric models, to evaluate the impacts of climate change. We also assessed the overlap between potential distribution and protected areas to aid conservation strategies. Using 319 georeferenced herbarium specimens, seven bioclimatic variables, three edaphic variables, and elevation, we applied the MaxEnt algorithm. Results showed an important retraction in suitable areas for all species (approximately -50%). Three species will overlap with protected areas in the future, but Chacoan and Espinal species S. acanthoclada and S. spiniflora inhabit highly anthropized habitats with insufficient actual and future protection. Therefore, we propose in situ and ex situ conservation strategies. These findings highlight the vulnerability of xerophytic taxa in southern South America under climate change.