Many semi-arid plant communities in western North America are dominated by big sagebrush. These ecosystems are being reduced in extent and quality due to economic development, invasive species, and climate change. These pervasive modifications have generated concern about the long-term viability of sagebrush habitat and sagebrush-obligate wildlife species (notably Greater Sage-Grouse), highlighting the need for better understanding of the future big sagebrush distribution, particularly at the species' range margins. The leading and trailing edges of potential climate-driven distribution shifts are likely to be areas most sensitive to climate change. Although several processes contribute to distribution shifts, regeneration is a fundamental requirement, especially for species with episodic regeneration patterns, such as big sagebrush. We used a process-based regeneration model for big sagebrush to simulate potential germination and seedling survival in response to climatic and edaphic conditions. We estimated current and future regeneration under 2070–2099 CMIP5 climate conditions at trailing and leading edges that were previously identified using traditional species distribution models. Our results supported expectations of increased probability of regeneration at the leading edge and decreased probability at the trailing edge compared to current levels. Our simulations indicated that soil water dynamics at the leading edge will become more similar to the typical seasonal ecohydrological conditions observed within the current range of big sagebrush. At the trailing edge, increased winter and spring dryness represented a departure from conditions typically supportive of big sagebrush. Our results highlighted that minimum and maximum daily temperatures as well as soil water recharge and summer dry periods are important constraints for big sagebrush regeneration. We observed reliable changes in areas identified as trailing and leading edges, consistent with previous predictions. However, we also identified potential local refugia within the trailing edge, mostly at higher elevation sites. Decreasing regeneration probability at the trailing edge suggests that it will be difficult to preserve and/or restore big sagebrush in these areas. Conversely, increasing regeneration probability at the leading edge suggests a growing potential for conflicts in management goals between maintaining existing grasslands and croplands by preventing sagebrush expansion versus accepting a shift in plant community composition to sagebrush dominance.