Climate change has the potential to directly and indirectly affect river ecosystems. Direct effects influence key ecological drivers, such as variation in temperature and rainfall and hence runoff. Indirect effects include changes to vegetation cover and land and water management practices. In some locations, these indirect effects are potentially a greater threat than the direct drivers that are the focus of much climate change research. An additional concern is whether changes in land-use and water management will interact with changes in climate to cause impacts larger than those expected by climate change alone. To better understand the range of potential futures for rivers in the Tasmanian Midlands, we modelled river flows and temperature under a number of scenarios that incorporate potential direct and indirect effects of climate change, as well as plans for a new irrigation scheme. Outputs from these models were used as inputs to Bayesian Networks designed to predict changes in condition of key river ecosystem components. Our results suggest that the biggest threat facing the Tasmanian Midlands is the projected increase in river temperatures across the entire region. Our projections for impacts on hydrology varied spatially, with some river reaches expected to see a marked decline in condition, while other reaches could potentially benefit from ‘shandying’ of transferred water and through storage of winter flows for summer release. These results have been incorporated into a spatial multi-criteria analysis tool that facilitates their use in decision making and for an analysis designed to identify potential climate refuges.