Variations in global patterns of burning and fire regimes are relatively well measured, however, the degree of influence of the complex suite of biophysical and human drivers of fire remains controversial and incompletely understood. Such an understanding is required in order to support current fire management and to predict the future trajectory of global fire patterns in response to changes in these determinants. In this study we explore and compare the effects of four fundamental controls on fire, namely the production of biomass, its drying, the influence of weather on the spread of fire and sources of ignition. Our study area is southern Australia, where fire is currently limited by either fuel production or fuel dryness. As in most fire-prone environments, the majority of annual burned area is due to a relatively small number of large fires. We train and test an Artificial Neural Network’s ability to predict spatial patterns in the probability of large fires (>1,250 ha) in forests and grasslands as a function of proxies of the four major controls on fire activity. Fuel load is represented by predicted forested biomass and remotely sensed grass biomass, drying is represented by fraction of the time monthly potential evapotranspiration exceeds precipitation, weather is represented by the frequency of severe fire weather conditions and ignitions are represented by the average annual density of reported ignitions. The response of fire to these drivers is often non-linear. Our results suggest that fuel management will have limited capacity to alter future fire occurrence unless it yields landscape-scale changes in fuel amount, and that shifts between, rather than within, vegetation community types may be more important. We also find that increased frequency of severe fire weather could increase the likelihood of large fires in forests but decrease it in grasslands. These results have the potential to support long-term strategic planning and risk assessment by fire management agencies.