Variation in the frequency, extent and intensity of wildfires can drive changes in the composition, structure, diversity and functioning of ecosystems in fire-prone regions worldwide. However, relationships between climatic variation and wildfire occurrence remain poorly understood in many fire-prone regions. We investigated fire occurrence and extent across 15,500 km2 of semi-arid southwest Australia in relation to inter-annual and/or seasonal variation in regional climate and broad-scale circulation patterns. Superposed epoch analysis (SEA) was used to determine whether wildfire occurrence was related to anomalously high or low regional rainfall or temperature. In particular, we tested if years of minor fire extent (i.e., <250 km2 burnt) and major fire extent (i.e., >1,000 km2 burnt) occurred under different climatic conditions. We also used SEA to determine if wildfires occurred during or following periods of extremes of drivers of regional climate, including the El Niño southern oscillation (ENSO), the Indian Ocean dipole, atmospheric blocking in the adjacent Southern Ocean, and the southern annular mode (SAM). Fire occurrence was linked to dry and hot conditions typically associated with the El Niño phase of ENSO, with few or no fires in years with cool and wet summers. However, major fire years tended to occur during drought conditions that followed wet and cool conditions in spring and summer of the preceding year. These wet and cool periods were typically associated with the presence of blocking highs in the Southern Ocean to the south of Western Australia. We hypothesise that high rainfall in spring and summer favours the growth of ephemeral plants while subsequent drought conditions promote fuel drying, resulting in more continuous and highly flammable fuel beds capable of sustaining larger fires. Regional climatic patterns are likely driven by interactions among the SAM, atmospheric blocking, and decaying tropical cyclones. As climatic extremes are expected to increase in intensity and frequency in the future, it is likely that the occurrence of extensive wildfires in semi-arid southwest Australia will also increase, potentially driving changes in the distribution and composition of fire-sensitive plant communities.