The lower Athabasca River (Canada) has experienced notable declines in streamflow and increasing oil sands development since the 1970s. This study investigates the potential impacts of climate change on navigability using both observed historical and projected future flows derived via hydrological simulations driven by an ensemble of statistically downscaled general circulation model climate data. Our use of proposed indices that form the Aboriginal Navigation Index (ANI) and a new index based on percentage over threshold (POT) occurrences yielded novel insights into anticipated changes to the flow regime. Comparisons of near (2041–2070) and far (2071–2100) future periods with the historical baseline (1981–2010) yielded results that project significant reductions in the 500 m3 s−1 POT during the fall navigability period spanning weeks 34 to 43, as well as reductions in the integrated ANIFall. These results indicate that challenging navigational conditions may become more frequent in the second half of the 21st century, not only during this fall period but also earlier into the summer, due to a shift in the flow regime, with potentially severe impacts on the users of the river channels. Our assessment approach is transferable to other regional study areas and should be considered in water management and environmental flow frameworks.