The management of freshwater ecosystems is usually targeted through the regulation of water quantity (limiting diversions and providing environmental flows) and regulation of water quality (setting limits or targets for constituent concentrations). Climate change is likely to affect water quantity and quality in multiple ways and the future management of freshwater ecosystems requires predictions of plausible future conditions. We use a suite of ecologically-relevant hydrological indicators to determine the significance of projected climate-driven hydrological changes in the Upper Murrumbidgee River Catchment in south eastern Australia in relation to river regulation. We also determine the possible water quality changes (in relation to guidelines for aquatic ecosystem protection) associated with the climate change projections to identify the combined effects of hydrological and water quality changes. The results of this study suggest that river regulation has resulted in greater changes to ecologically-relevant streamflow characteristics than climate change scenarios that involve a 1 and 2 °C temperature rise in the Upper Murrumbidgee River Catchment. In contrast to the projected hydrological changes, Bayesian Network modelling suggests very small changes to violations of water quality thresholds designed to protect aquatic ecosystems as a result of climate change. By identifying key components of the flow and water quality regimes that may be affected by climate change, we are able to provide managers with information that assists in developing adaptation initiatives.