National-scale analyses of fire occurrence are needed to prioritize fire policy and management activities across the United States. However, the drivers of national-scale patterns of fire occurrence are not well understood, and how the relative importance of human or biophysical factors varies across the country is unclear. Our research goal was to model the drivers of fire occurrence within ecoregions across the conterminous United States. We used generalized linear models to compare the relative influence of human, vegetation, climate, and topographic variables on fire occurrence in the United States, as measured by MODIS active fire detections collected between 2000 and 2006. We constructed models for all fires and for large fires only and generated predictive maps to quantify fire occurrence probabilities. Areas with high fire occurrence probabilities were widespread in the Southeast, and localized in the Mountain West, particularly in southern California, Arizona, and New Mexico. Probabilities for large-fire occurrence were generally lower, but hot spots existed in the western and south-central United States The probability of fire occurrence is a critical component of fire risk assessments, in addition to vegetation type, fire behavior, and the values at risk. Many of the hot spots we identified have extensive development in the wildland–urban interface and are near large metropolitan areas. Our results demonstrated that human variables were important predictors of both all fires and large fires and frequently exhibited nonlinear relationships. However, vegetation, climate, and topography were also significant variables in most ecoregions. If recent housing growth trends and fire occurrence patterns continue, these areas will continue to challenge policies and management efforts seeking to balance the risks generated by wildfires with the ecological benefits of fire.