Water temperature is a key determinant of biological processes in rivers. Temperature in northern latitude rivers is expected to increase under climate change, with potentially adverse consequences for cold water-adapted species. In Canada, little is currently known about the timescales or magnitude of river temperature change, particularly in large (≥104 km2) watersheds. However, because Canadian watersheds are home to a large number of temperature-sensitive organisms, there is a pressing need to understand the potential impacts of climate change on thermal habitats. This paper presents the results of a study to simulate the effects of climate change on the thermal regime of the lower Saint John River (SJR), a large, heavily impounded, socio-economically important watershed in eastern Canada. The CEQUEAU hydrological-water temperature model was calibrated against river temperature observations and driven using meteorological projections from a series of regional climate models. Changes in water temperature were assessed for three future periods (2030–2034, 2070–2074 and 2095–2099). Results show that mean water temperature in the SJR will increase by approximately ~1 °C by 2070–2074 and a further ~1 °C by 2095–2099, with similar findings for the maximum, minimum and standard deviation. We calculated a range of temperature metrics pertaining to the Atlantic Salmon and Striped Bass, key species within the SJR. Results show that while the SJR will become increasingly thermally-limiting for Atlantic Salmon, the Striped Bass growth season may actually lengthen under climate change. These results provide an insight into how climate change may affect thermal habitats for fish in eastern Canadian rivers.