Blackwater contains high levels of dissolved organic carbon that can be rapidly consumed by microbes, sometimes leading to extremely low levels of dissolved oxygen (hypoxia) and drastic consequences for aquatic life, including fish kills. Drought-breaking rains in late 2010 inundated large areas of the Barmah–Millewa Forest, southern Murray–Darling Basin, Australia, and resulted in a prolonged hypoxic blackwater event within the forest and the Murray River downstream. This study investigated the short-term effects of the blackwater event on fish and crayfish. Compared with non-affected sites, blackwater affected sites had: significantly higher abundances of emerged Murray crayfish (Euastacus armatus) that were vulnerable to desiccation, predation and exploitation; large numbers of dead or dying shrimp and yabbies; significantly reduced abundances of native fish; but contained similar abundances of alien fish species (particularly common carp, Cyprinus carpio). The nature of the mechanisms that caused these changes and the longer term significance of the event on the river system remains an important area for future research. We also propose a range of management considerations for reducing the blackwater impacts, such as the timing of environmental water delivery after prolonged drought and the importance of maintaining river–floodplain connectivity during flood periods.