Climate extremes such as floods and droughts are reshaping ecosystems globally, causing rapid shifts in ecosystem structure and functioning. The Coorong, Lower Lakes and Murray Mouth region, located at the end of the River Murray, is one of Australia’s most ecologically significant wetland systems. It supports a mosaic of freshwater, estuarine, and marine habitats, but has experienced substantial ecological change due to river regulation, water extraction and intensifying climate extremes, including major floods and prolonged droughts such as the Millennium Drought. We conducted a systematic literature review to assess the hydrological drivers and ecological responses across key biological groups, including fishes, vegetation, plankton, benthic invertebrates and microbes, before and after extreme events. This synthesis identifies patterns of hydrological and ecological change and introduces a conceptual framework to interpret biological responses to climate extremes. The findings aim to inform more adaptive, ecosystem-based water management and improve preparedness for future climate variability in this nationally significant wetland system.