The recent widespread mountain pine beetle (MPB) outbreak in the Southern Rocky Mountains presents an opportunity to investigate the relative influence of anthropogenic, biologic, and physical drivers that have shaped the spatiotemporal patterns of the outbreak. The aim of this study was to quantify the landscape-level drivers that explained the dynamic patterns of MPB mortality, and simulate areas with future potential MPB mortality under projected climate-change scenarios in Grand County, Colorado, USA. The outbreak patterns of MPB were characterized by analysis of a decade-long Landsat time-series stack, aided by automatic attribution of change detected by the Landsat-based Detection of Trends in Disturbance and Recovery algorithm (LandTrendr). The annual area of new MPB mortality was then related to a suite of anthropogenic, biologic, and physical predictor variables under a general linear model (GLM) framework. Data from years 2001–2005 were used to train the model and data from years 2006–2011 were retained for validation. After stepwise removal of non-significant predictors, the remaining predictors in the GLM indicated that neighborhood mortality, winter mean temperature anomaly, and residential housing density were positively associated with MPB mortality, whereas summer precipitation was negatively related. The final model had an average area under the curve (AUC) of a receiver operating characteristic plot value of 0.72 in predicting the annual area of new mortality for the independent validation years, and the mean deviation from the base maps in the MPB mortality areal estimates was around 5%. The extent of MPB mortality will likely expand under two climate-change scenarios (RCP 4.5 and 8.5) in Grand County, which implies that the impacts of MPB outbreaks on vegetation composition and structure, and ecosystem functioning are likely to increase in the future.