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Climate change has emerged as one of the most potent threats to forests across the globe. This study examined the exposure and sensitivity of ponderosa pine (Pinus ponderosa) to climate change from landscape to continental scales across its geographic range in western North America. We began by developing a framework for assessing climate change exposure based on climatic water deficit (CWD), a metric of unmet evaporative demand and strong predictor of plant species distributions. The framework combined change in average annual CWD and frequency of departure from the local historical range of variability in annual CWD. We applied this framework to Tejon Ranch, a mountainous landscape in the Tehachapi Mountains of Southern California. We found disproportionate climate change exposure at high elevations due to projected losses in snowpack associated with warmer winters. Next, we assessed long-term relationships between climate and ponderosa pine growth at Tejon Ranch. Interannual variability in tree growth was explained by a combination of climatic water deficit over the current and preceding water-year (Oct 1 – Sep 30), March precipitation, July maximum and January minimum air temperatures (adjusted R² = 0.55-0.57). In general, growth is expected to decline under future climate change in current stands, but heterogeneous topography offered potential favorable growing habitat under all climate projections, particularly on north-facing slopes at higher elevations. Under warmer and drier projections, overall habitat availability decreased in terms of distance to the nearest suitable patch from current stands for both mid- (2040-2069) and end-of-century (2070-2099) periods. Spatiotemporal climate variability, however, created suitable patches within average seed dispersal distance of current stands, potentially offering ephemeral windows of opportunity for local range shifts without long-distance dispersal. Finally, we examined the sensitivity of ponderosa pine to climate variability across its range in western North America by combining the Tejon Ranch tree rings and 159 published chronologies from the International Tree Ring Data Bank. We encountered heterogeneous climate sensitivities across the species range to a suite of limiting climate variables. Our results indicated that position along environmental gradients interacts with genetically based local adaptation to determine climate sensitivity of individual ponderosa pine populations. Although all ponderosa pine populations will likely be exposed to locally novel climate regimes in the 21st Century, the species’ overall wide variability in climate sensitivity will likely buffer some populations from negative effects of climate change. Future conservation efforts for ponderosa pine and other wide-ranging species should consider the mediating role of geographic patterns of genetic structure in within-species climate sensitivities.