Five metal mixture dose–response models were used to predict the toxicity of porewater to young sturgeon at areas of interest in the Upper Columbia River (WA, USA/BC, Canada) and to evaluate these models as tools for risk assessments. Dose components of metal mixture models included exposure to free metal ion activities or metal accumulation by biotic ligands or humic acid, and links of dose to response used logistic equations, independent joint action equations, or additive toxicity functions. Laboratory bioassay studies of single metal exposures to juvenile sturgeon, porewater collected in situ in the fast-flowing Upper Columbia River, and metal mixture models were used to evaluate toxicity. The five metal mixture models were very similar in their predictions of adverse response of juvenile sturgeon and in identifying copper (Cu) as the metal responsible for the most toxic conditions. Although the modes of toxic action and the 20% effective concentration values were different among the dose models, predictions of adverse response were consistent among models because all doses were tied to the same biological responses. All models indicated that 56% ± 5% of 122 porewater samples were predicted to have <20% adverse response, 25% ± 5% of samples were predicted to have 20% to 80% adverse response, and 20% ± 4% were predicted to have >80% adverse response in juvenile sturgeon. The approach of combining bioassay toxicity data, compositions of field porewater, and metal mixture models to predict lack of growth and survival of aquatic organisms due to metal toxicity is an important tool that can be integrated with other information (e.g., survey studies of organism populations, life cycle and behavior characteristics, sediment geochemistry, and food sources) to assess risks to aquatic organisms in metal-enriched ecosystems. Environ Toxicol Chem 2023;00:1–12. Published 2023. This article is a U.S. Government work and is in the public domain in the USA.