Identifying and tracking the influence of industrial activities on streams and lakes is a priority for monitoring in Canada’s oil sands region (OSR). While differences in indicators are often found in waterbodies adjacent to mining facilities, the confounding influence of natural exposures to bitumen and other stressors can affect the identification of industrial effects. However, recent work suggests metrics of industrial activity at individual facilities, including production and fuel consumption, may be used in site-specific analyses to identify influence of the industry as a whole as well as individual operations. This study further examined the potential relationships between industrial and climatic variables on benthic communities from 13 streams and 4 lakes using publicly available data from the minable region and the Elastic Net (EN) variable selection technique. From the full set of possible industrial and climate variables, the EN commonly identified the negative influence of plant and fuel use of petroleum coke at the Suncor Basemine on benthic communities in streams and lakes. The fuel/plant use of petroleum coke at Suncor likely reflects the emission and regional deposition of delayed coke fly ash. Among the other industrial variables, crude bitumen production at Syncrude Mildred Lake and other facilities, steam injection rates, and petroleum coke stockpiling were also selected for some benthic invertebrate indices at some sites. Land disturbance metrics were also occasionally selected, but the analyses largely support the predominant influence of industrial facilities via (inferred) atmospheric pathways. While climate variables were also commonly selected by EN and follow-up work is needed, this study suggests that integrating industrial performance data into analyses of biota using a site-specific approach may have broad applicability in environmental monitoring in the OSR. More specifically, the approach used here may both resolve the long-standing challenge of natural confounding influences on monitoring the status of streams in the OSR and track the influence of industrial activities in biota below critical effect sizes.