Large wildfires (>40 ha) account for the majority of burned area across the contiguous United States (US) and appropriate substantial suppression resources. A variety of environmental and social factors influence wildfire growth and whether a fire overcomes initial attack efforts and becomes a large wildfire. However, little is known about how these factors differ between lightning-caused and human-caused wildfires. This study examines differences in temperature, vapour pressure deficit, fuel moisture and wind speed for large and small lightning- and human-caused wildfires during the initial days of fire activity at ecoregion scales across the US. Large fires of both human and lightning origin occurred coincident with above-normal temperature and vapour pressure deficit and below-normal 100-hour dead fuel moisture compared with small fires. Large human-caused wildfires occurred, on average, coincident with higher wind speeds than small human-caused wildfires and large lightning-caused wildfires. These results suggest the importance of winds in driving rapid fire growth that can allow fires to overcome many of the factors that typically inhibit large human-caused fires. Additionally, such findings highlight the interplay between human activity and meteorological conditions and the importance of incorporating winds in modelling large-fire risk in human-dominated landscapes.