This study aims to assess the potential alterations in the hydrological regime attributed to projected climate change in one of the largest rivers in the Carpathian Area, the Mures River, and to estimate associated threats to riverine ecosystem. The eco-hydrological model, Soil and Water Integrated Model (SWIM), was applied on the Mures River basin, calibrated and validated against records at a gauging station in Alba-Julia town. A set of nine future projections for climatic parameters under one emissions scenario A1B over the period 1971–2100 were fed into the SWIM model. To provide functional link between hydrological regimes and riverine ecosystems, each of the nine simulated discharge time series were introduced into the IHA (Indicators of Hydrological Alterations) tool. Triggered changes in hydrological patterns of the Mures River were assessed at the basin and sub-basin scales. The obtained results present a strong agreement through all nine climate projections; suggesting an increase in the discharge of Mures River for the winter season; a decrease in summer and prolongation of the low flow periods by the end of the century. Anticipated changes would pose threats to aquatic ecosystems; altering normal life-cycles; and depleting natural habitats of species.