Climate change has emerged as a major threat to biodiversity, but there have been few assessments of variability in sensitivity to climate across species’ ranges. We examined the sensitivity of ponderosa pine (Pinus ponderosa), a common, commercially important tree species found throughout the western United States, to climate variability using tree rings mostly from the International Tree Ring Data Bank (161 chronologies) and multiple climate products for 1930–1979. We compared interannual tree ring variation to water-year precipitation (wy ppt), May-July vapor pressure deficit (MJJ VPD), April-July precipitation (AMJJ ppt) and average winter (Dec-Feb) minimum temperature (winter tmn). We mapped growth-climate correlations for each variable and applied hierarchical agglomerative cluster analysis to identify five main groups of climate sensitivities, one of which contained mostly climate-insensitive populations. Ponderosa pine growth was positively correlated with wy ppt and AMJJ ppt and negatively correlated with MJJ VPD throughout its range, but sensitivities were greater in the Southern Rockies and Northern Great Plains than in Pacific and Southwestern populations. Sensitivities to winter tmn were weaker than responses to other climate variables, but Pacific and interior populations mostly demonstrated positive and negative responses, respectively. In summary, our analyses revealed the general pattern that interior populations of ponderosa pine were more climate-sensitive than Pacific populations, but there is considerable heterogeneity in sensitivity throughout the species’ range. Sensitivities to climate variables were related to position along corresponding climate gradients for all variables except MJJ VPD, but the unevenness of these relationships suggests a role of local adaptation. Our results illustrate the variation in climate response for a uniquely wide-ranging species and suggest that “leading” and “trailing” range edge concepts can oversimplify patterns of species exposure to climate change.