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Dendroecology provides a means to evaluate how mature trees have responded to climate stresses in the recent past and provides one approach for projecting how existing forests will respond to future climate change. This study documented spatial variation in the strength of growth-climate associations for six oak (Quercus) species at 284 sites in eastern North America that span substantial gradients of temperature and site water balance. Radial growth of oaks was more strongly related to growing-season precipitation and the ratio of precipitation to potential evapotranspiration at sites in the western part of the study region where drought conditions occur more frequently. Growth was more strongly related to growing-season mean maximum temperature in the warmer, southern part of the study region. Growth of oaks was not strongly related to site water balance or temperature in the northeastern part of the study region. These results indicate that if climate change results in increased growing-season drought stress, this will adversely affect mature oak trees growing in the southern and western parts of eastern North America, but oaks growing in northeastern North America have more safe space for change before they will suffer reduced growth and vigor.