Estuaries and lagoons are subject to salinity fluctuations from variable riverine inflow of freshwater. Reduced freshwater flow can cause hypersaline conditions, which can reach extreme levels in lagoons and microtidal estuaries, and effect biota. Macroinvertebrates play a major role in estuarine and lagoon ecosystems, as prey for higher trophic levels and by providing crucial ecological functions. Yet, when salinities exceed the species’ tolerance limits, they are lost from sediments, with impacts for ecosystem functions and services. The Coorong in South Australia comprises an estuary and lagoon with an extreme salinity gradient, where salinities vary subject to water management. To inform environmental management, we performed threshold indicator taxa analysis (TITAN) for macroinvertebrates, based on a long-term (>10 years) monitoring data base. We present indicator species change points (thresholds) for 16 macroinvertebrate taxa, of which twelve were vulnerable to increasing salinities, and four tolerant to salinities >50. Two community level change points were identified at a salinity of 25 and of 64, which were also detected by multivariate regression analyses. Restoration and improvement of ecological conditions centres around optimal salinity targets for various ecosystem components and outcomes from TITAN provide valuable ecological threshold information.