Conservation of large carnivore populations requires effective management strategies that promote landscape-scale protection and genetic connectivity. Pivotal to the success of these strategies is sufficient evidence, including quantifying the processes that govern species distribution. We used telemetry data from 63 lions from the Kavango-Zambezi Transfrontier Conservation Area (KAZA TFCA) in southern Africa to analyze inter-demographic differences in habitat relationships using a mixed-effects resource selection analysis approach. In this semi-arid landscape, some of the most important drivers of habitat selection are surface water and precipitation, which in turn regulate prey abundance. Predicted relative probability of habitat selection was highest near water irrespective of age and sex; however, the effect of precipitation varied depending on the demographic class. Adult lions and subadult females preferred habitat with above average rainfall; however, the opposite was true for subadult males which showed a strong aversion to precipitation. Across all four demographic classes, relative probability of habitat selection was generally positively associated with higher levels of prey abundance with the exception of gemsbok which was negatively correlated with adult female, subadult male, and subadult female habitat use. The predicted distributions for all four demographic classes were widespread across multiple different land-use types, highlighting the need to extend the traditional concept of formally protected areas to include multi-use landscapes and support large-scale transboundary conservation initiatives.