Down-the-drain chemical spills that reach a sewage treatment plant (STP) can cause a biological “toxic shock” that may reduce or eliminate the capability of STP microorganisms to remove organic matter and nutrients for weeks to months. Thus, chemical spills are a threat to water quality. Here, we present a case study of toxic shock threat prioritization for chemicals used at industrial facilities connected to the Käppala STP in Stockholm, Sweden. We surveyed 60 facilities, collected information on the use and storage of bulk chemical products, and documented 8676 uses of constituent chemicals. In situ chemical tracer experiments were conducted in the primary sewer tunnel leading to Käppala to measure chemical spill dilution during transit to the plant. To assess chemical risks to the plant, we extracted data on toxicity to STP microorganisms for 6168 chemicals from European Chemicals Agency brief profiles and estimated exposure concentrations in the plant using conservative assumptions. Under a high-end spill scenario, the majority of chemicals in the survey posed a negligible risk for adverse effects on plant microorganisms, however 28 chemicals were identified as posing a potential risk and were prioritized for additional information gathering to refine our conservative assumptions. The analysis framework was built into an online tool (RAVEN STREAM) provided as free, open-source software for STP operators to screen for threats posed by possible chemical spills at connected facilities. The threat identification framework can facilitate communication between STPs and their upstream industrial clients to mitigate possible high-risk chemical spills before they happen.