Livestock predation and associated human-carnivore conflicts are increasing worldwide and require the development of methods and concepts for risk assessment and conflict management. Here we use knowledge on habitat preference and distribution of pumas and provide a first assessment of the spatial risk of livestock to puma depredation in Patagonian ranches, Argentina. In an initial step, we developed a rule-based habitat model in a Geographic Information System (GIS) to predict the distribution of puma habitat at a regional scale in Patagonia. We then used empirically derived puma occurrence records from Patagonian ranches 1) to test our regional habitat predictions, and 2) to evaluate if paddock characteristics (vegetation cover, topography, and distance to roads) contribute to explain puma occurrences within ranches. Finally, we simulated three livestock management scenarios differing in their spatial and seasonal allocation of livestock to paddocks, and compared the likelihood of livestock exposure to pumas among scenarios. At a regional scale, 22% of the study region was predicted to be suitable for puma home ranges. The greatest uncertainty in these predictions resulted from assumptions on woody vegetation cover requirements at the home range scale. Within ranches, puma occurrences were positively associated with paddock topography, woody vegetation cover on paddocks, and proximity to predicted regional puma habitat. Comparing the risk of predation by puma among simulated livestock management scenarios implied that rotating livestock during seasons may help to reduce the likelihood of livestock exposure to pumas. Our results show the usefulness of rule-based habitat models for describing broad-scale carnivore distributions and for aiding risk assessments to mitigate conflicts between predators and human activities.