Large fires account for the majority of burned area and are an important focus of fire management. However, ‘large’ is typically defined by a fire size threshold, minimizing the importance of proportionally large fires in less fire-prone ecoregions. Here, we defined ‘large fires’ as the largest 10% of wildfires by ecoregion (n = 175,222 wildfires from 1992 to 2015) across the United States (U.S.). Across ecoregions, we compared fire size, seasonality, and environmental conditions (e.g., wind speed, fuel moisture, biomass, vegetation type) of large human- and lighting-started fires that required a suppression response. Mean large fire size varied by three orders of magnitude: from 1 to 10 ha in the Northeast vs. >1000 ha in the West. Humans ignited four times as many large fires as lightning, and were the dominant source of large fires in the eastern and western U.S. (starting 92% and 65% of fires, respectively). Humans started 80,896 large fires in seasons when lightning-ignited fires were rare. Large human-started fires occurred in locations and months of significantly higher fuel moisture and wind speed than large lightning-started fires. National-scale fire policy should consider risks to ecosystems and economies by these proportionally large fires and include human drivers in large fire risk assessment.