Novel forest decline is increasing due to global environmental change, yet the causal factors and their interactions remain poorly understood. Using tree ring analyses, we show how climate and multiple biotic factors caused the decline of whitebark pine (Pinus albicaulis) in 16 stands in the southern Canadian Rockies. In our study area, 72% of whitebark pines were dead and 18% had partially dead crowns. Tree mortality peaked in the 1970s; however, the annual basal area increment of disturbed trees began to decline significantly in the late 1940s. Growth decline persisted up to 30 years before trees died from mountain pine beetle (Dendroctonus ponderosae), Ips spp. bark beetles or non-native blister rust pathogen (Cronartium ribicola). Climate-growth relations varied over time and differed among the healthy and disturbed subpopulations of whitebark pine. Prior to the 1940s, cool temperatures limited the growth of all subpopulations. Growth of live, healthy trees became limited by drought during the cool phase (1947 -1976) of the Pacific Decadal Oscillation (PDO) and then reverted to positive correlations with temperature during the subsequent warm PDO phase. In the 1940s, the climate-growth relations of the disturbed subpopulations diverged from the live, healthy trees with trees ultimately killed by mountain pine beetle diverging the most. We propose that multiple factors interacted over several decades to cause unprecedented rates of whitebark pine mortality. Climatic variation during the cool PDO phase caused drought stress that may have predisposed trees to blister rust. Subsequent decline in snowpack and warming temperatures likely incited further climatic stress and with blister rust reduced tree resistance to bark beetles. Ultimately, bark beetles and blister rust contributed to tree death. Our findings suggest the complexity of whitebark pine decline and the importance of considering multiway drought-disease-insect interactions over various timescales when interpreting forest decline.