Open-pit and subsurface extraction of oil sands in Alberta, Canada, continue to expand and pose a risk of contamination to the aquatic ecosystems of the region. These operations have raised wider concerns the design of the ongoing environmental monitoring may be insufficient to detect large-scale trends. Our goal was to advance assessment of ecological risk within the region using a combination of approaches, first by quantifying hazards associated with single and multiple contaminants of concern, and second to map expected risk based on spatial and environmental associations, thereby identifying areas of possible impact in the oil sands region that could support adaptive monitoring by assessing and mapping exceedance of guideline values. We assessed 17 dissolved metals of concern at 19 mainstem and tributary monitoring stations on the Lower Athabasca River. Exceedances of guideline values were transient and spatially-restricted, meaning risk was generally low to negligible for many contaminants and sampling stations. The joint or combined risk at least one contaminant would exceed their respective (long-term) guideline values was greatest at Big Creek (32%), but again, typically low for the majority of monitoring stations. However high temporal stochasticity meant statistical associations among monitoring stations were weak, and as a result the association between predicted concentrations and ecological risk could not be expanded beyond these point measurements. Despite this limitation, the synthesis of various lines of evidence indicated that contaminant delivery is measurable and cumulative in proximity to mining developments, and that there is some evidence of ecological effects linked to contaminant exposure. The results of the ERA and the challenges encountered in this work should be used to inform future monitoring and research as part of the adaptive management framework to improve the ERA process to ensure that the monitoring program is effective and viable in the long-term.