Structure loss is an acute, costly impact of the wildfire crisis in the western conterminous United States (“West”), motivating the need to understand recent trends and causes. We document a 246% rise in West-wide structure loss from wildfires between 1999–2009 and 2010–2020, driven strongly by events in 2017, 2018, and 2020. Increased structure loss was not due to increased area burned alone. Wildfires became significantly more destructive, with a 160% higher structure-loss rate (loss/kha burned) over the past decade. Structure loss was driven primarily by wildfires from unplanned human-related ignitions (e.g. backyard burning, power lines, etc.), which accounted for 76% of all structure loss and resulted in 10 times more structures destroyed per unit area burned compared with lightning-ignited fires. Annual structure loss was well explained by area burned from human-related ignitions, while decadal structure loss was explained by state-level structure abundance in flammable vegetation. Both predictors increased over recent decades and likely interacted with increased fuel aridity to drive structure-loss trends. While states are diverse in patterns and trends, nearly all experienced more burning from human-related ignitions and/or higher structure-loss rates, particularly California, Washington, and Oregon. Our findings highlight how fire regimes—characteristics of fire over space and time—are fundamentally social-ecological phenomena. By resolving the diversity of Western fire regimes, our work informs regionally appropriate mitigation and adaptation strategies. With millions of structures with high fire risk, reducing human-related ignitions and rethinking how we build are critical for preventing future wildfire disasters.