Anthropogenic pressure in areas of biodiversity importance erodes the integrity of the ecosystems they harbour, making features of biodiversity less buffered against extreme climatic events. We define the combination of these disturbances as compound events. We assessed compound event risk in protected areas (PAs) applying a spatial framework guided by criteria and quantitative thresholds associated with exposure to cyclones, drought, and intense human pressure. This assessment was used in a relational matrix to classify PAs with different risk of compound event occurrence. We identified PAs of higher conservation concern by quantifying the extent of human pressure in their surrounding landscape while harbouring large numbers of threatened vertebrate species. Of the 39,694 PAs assessed, very high risk of compound events was determined for 6965 PAs (17.5 %) related to cyclones and human pressure (mainly island hotspots), 6367 PAs (16 %) related to droughts and human pressure (island and continental hotspots), and 2031 PAs (5 %) to cyclones, drought and human pressure (mainly in island hotspots). From the subset of 2031 PAs assessed at very high risk, we identified 239 PAs of higher conservation concern distributed predominantly in the Caribbean Islands, Japan, North America Coastal Plain, Philippines, and Southwest Australia. Our work highlights PAs in the biodiversity hotspots where high risk of compound event occurrence poses a greater threat to species. We encourage researchers to adapt and apply this framework across other globally significant sites for conserving biodiversity to identify high risk-prone areas, and prevent further biodiversity decline.