Trends and variability in the hydrologic regime of the Athabasca River region were analyzed. Twenty hydrologic variables were selected for flow analysis within both the Athabasca River Basin (ARB) and, for comparison, surrounding watersheds. Intra- and inter-basin scale analyses were performed, including a comparison of changes in streamflow at stations forming part of the Reference Hydrometric Basin Network (RHBN) and non-designated gauges. Streamflow trends were also compared with trends in air temperature and precipitation over the entire Athabasca and surroundings study region. Noteworthy results include strong decreasing trends in annual, warm season (March to October) and summer month flows over the majority of the study region, in addition to a greater number of decreasing trends in Athabasca watershed flows compared to the surrounding basins. The timing of the spring freshet was found to have not shifted toward an earlier onset, contrary to results from previous studies. Lastly, trends in streamflow were similar to those for precipitation over the ARB and surrounding region, but did not relate strongly to trends in air temperature. The results of this study should be of assistance to water- resources managers and policy makers in making decisions about water use in this rapidly changing watershed.