Anthropogenic pressure is increasing the variety and frequency of environmental disturbance events, limiting recovery and leading to long-term declines in wild plant and animal populations. Coral reefs and associated fish assemblages are inherently dynamic due to their susceptibility to a host of disturbances, but regional-scale nuances in the drivers of long-term change frequently remain poorly resolved. Here, we examine the effects of multiple potential drivers of change in coral reef fish assemblages across 4 inshore regions of the Great Barrier Reef Marine Park (GBRMP), Australia, over 12-14 years (2007-2021). Each region had a unique disturbance history, in conjunction with long-term changes in physical and habitat variables. Phases of recovery were apparent in the years between disturbance events at all locations, but these were not long enough to prevent substantial declines in reef fish density (by 33%-72%) and species richness (by 41%-75%) throughout the study period. The main drivers of change in fish assemblages varied among regions; however, the most rapid changes followed cyclone and flood events. Limited recovery periods resulted in temporal shifts in fish species composition from typically coral-associated to algae-associated. Most trophic groups declined in density except farmers, grazers, omnivores and parrotfish. No-take marine reserves (NTMRs) had small and inconsistent effects on total fish assemblages, but delivered benefits for fishery-targeted piscivores. Our findings suggest that coral reef responses to local stressors and cumulative escalating climate change impacts are highly variable at regional scales, and that small NTMRs are unlikely to mitigate the impacts of increasingly frequent climatic disturbances. Nearshore coral reefs worldwide are high-value habitats that are either already degraded or vulnerable to degradation and the loss of important fish groups. Global efforts to reduce greenhouse gas emissions must be coupled with effective local management that can support the functioning and adaptive capacity of coral reefs.