This paper integrates dendrochronological, demographic, and experimental perspectives to improve understanding of the response of white spruce (Picea glauca (Moench) Voss) tree growth to climatic variability in interior Alaska. The dendrochronological analyses indicate that climate warming has led to widespread declines in white spruce growth throughout interior Alaska that have become more prevalent during the 20th century. Similarly, demographic studies show that white spruce tree growth is substantially limited by soil moisture availability in both mid- and late-successional stands. Interannual variability in tree growth among stands within a landscape exhibits greater synchrony than does growth of trees that occupy different landscapes, which agrees with dendrochronological findings that the responses depend on landscape position and prevailing climate. In contrast, the results from 18 years of a summer moisture limitation experiment showed that growth in midsuccessional upland stands was unaffected by moisture limitation and that moisture limitation decreased white spruce growth in floodplain stands where it was expected that growth would be less vulnerable because of tree access to river water. Taken together, the evidence from the different perspectives analyzed in this study clearly indicates that white spruce tree growth in interior Alaska is vulnerable to the effects of warming on plant water balance.