The resources available for managing wildfire risk are insufficient and ultimately finite , while the risk of catastrophic fires is enormous and growing. Prioritization of responses is thus critical, but the basis for comparing the costs and societal benefits of alternative investments in wildfire mitigation is woefully inadequate. Here, we assess and compare the costs of landscape-scale fuel treatment to the benefits of avoided destruction of property and smoke-related health impacts, and identify areas where the net benefits are greatest statewide. We find that re-prioritizing treatment areas could increase net benefits by a factor of more than 7 relative to historical treatments, with average net benefits in the top decile of areas (i.e., 28,000 km2) of >$225k per km2 (as compared to an estimated $90k per km2 of past treatments). By integrating physical, epidemiological, and economic methods, our results reveal large opportunities for improving the cost-effectiveness of wildfire fuel treatments, and demonstrate a general framework that can be applied by land managers in all wildfire-prone areas.