In recent decades, intense droughts, insect outbreaks, and wildfires have led to decreasing tree growth and increasing mortality in many temperate forests. We compared annual tree-ring width data from 1,097 populations in the coterminous United States to climate data and evaluated site-specific tree responses to climate variations throughout the 20th century. For each population, we developed a climate-driven growth equation by using climate records to predict annual ring widths. Forests within the southwestern United States appear particularly sensitive to drought and warmth. We input 21st century climate projections to the equations to predict growth responses. Our results suggest that if temperature and aridity rise as they are projected to, southwestern trees will experience substantially reduced growth during this century. As tree growth declines, mortality rates may increase at many sites. Increases in wildfires and bark-beetle outbreaks in the most recent decade are likely related to extreme drought and high temperatures during this period. Using satellite imagery and aerial survey data, we conservatively calculate that ≈2.7% of southwestern forest and woodland area experienced substantial mortality due to wildfires from 1984 to 2006, and ≈7.6% experienced mortality associated with bark beetles from 1997 to 2008. We estimate that up to ≈18% of southwestern forest area (excluding woodlands) experienced mortality due to bark beetles or wildfire during this period. Expected climatic changes will alter future forest productivity, disturbance regimes, and species ranges throughout the Southwest. Emerging knowledge of these impending transitions informs efforts to adaptively manage southwestern forests.