Greater sage-grouse (Centrocercus urophasianus; hereinafter, sage-grouse) are a sagebrush obligate species that has declined concomitantly with the loss and fragmentation of sagebrush ecosystems across most of its geographical range. The species currently is listed as a candidate for federal protection under the Endangered Species Act (ESA). Increasing wildfire frequency and changing climate frequently are identified as two environmental drivers that contribute to the decline of sage-grouse populations, yet few studies have rigorously quantified their effects on sage-grouse populations across broad spatial scales and long time periods. To help inform a threat assessment within the Great Basin for listing sage-grouse in 2015 under the ESA, we conducted an extensive analysis of wildfire and climatic effects on sage-grouse population growth derived from 30 years of lek-count data collected across the hydrographic Great Basin of Western North America. Annual (1984–2013) patterns of wildfire were derived from an extensive dataset of remotely sensed 30-meter imagery and precipitation derived from locally downscaled spatially explicit data. In the sagebrush ecosystem, underlying soil conditions also contribute strongly to variation in resilience to disturbance and resistance to plant community changes (R&R). Thus, we developed predictions from models of post-wildfire recovery and chronic effects of wildfire based on three spatially explicit R&R classes derived from soil moisture and temperature regimes. We found evidence of an interaction between the effects of wildfire (chronically affected burned area within 5 kilometers of a lek) and climatic conditions (spring through fall precipitation) after accounting for a consistent density-dependent effect. Specifically, burned areas near leks nullifies population growth that normally follows years with relatively high precipitation. In models, this effect results in long-term population declines for sage-grouse despite cyclic periods of high precipitation. Based on 30-year projections of burn and recovery rates, our population model predicted steady and substantial long-term declines in population size across the Great Basin. Further, example management scenarios that may help offset adverse wildfire effects are provided by models of varying levels of fire suppression and post-wildfire restoration that focus on areas especially important to sage-grouse populations. These models illustrate how sage-grouse population persistence likely will be compromised as sagebrush ecosystems and sage-grouse habitat are degraded by wildfire, especially in a warmer and drier climate, and by invasion of annual grasses that can increase wildfire frequency and size in the Great Basin.