Continued growth of the human population on Earth will increase pressure on already stressed terrestrial water resources required for drinking water, agriculture, and industry. This stress demands improved understanding of critical controls on water resource availability, particularly in water-limited regions. Mechanistic predictions of future water resource availability are needed because non-stationary conditions exist in the form of changing climatic conditions, land management paradigms, and ecological disturbance regimes. While historically ecological disturbances have been small and could be neglected relative to climatic effects, evidence is accumulating that ecological disturbances, particularly wildfire, can increase regional water availability. However, wildfire hydrologic impacts are typically estimated locally and at small spatial scales, via disparate measurement methods and analysis techniques, and outside the context of climate change projections. Consequently, the relative importance of climate change driven versus wildfire driven impacts on streamflow remains unknown across the western USA. Here we show that considering wildfire in modeling streamflow significantly improves model predictions. Mixed effects modeling attributed 2%−14% of long-term annual streamflow to wildfire effects. The importance of this wildfire-linked streamflow relative to predicted climate change-induced streamflow reductions ranged from 20%−370% of the streamflow decrease predicted to occur by 2050. The rate of post-wildfire vegetation recovery and the proportion of watershed area burned controlled the wildfire effect. Our results demonstrate that in large areas of the western USA affected by wildfire, regional predictions of future water availability are subject to greater structural uncertainty than previously thought. These results suggest that future streamflows may be underestimated in areas affected by increased prevalence of hydrologically relevant ecological disturbances such as wildfire.