Technological accidents triggered by natural hazards, which are commonly referred to as Natech events, are rare occurrences yet carry the potential for significant damage. Specifically, the release of hazardous chemicals into the aquatic environment and community water systems poses a grave threat to human health and society. Accordingly, we must conduct assessments that consider the potential consequences of these accidents. In this study, we examined the criteria for implementing spill protection measures to mitigate river spills of chemical substances using information on the amount of chemical substances and their toxicity. The countermeasure options readily available to employees at industrial plants and chemical storage sites where a chemical spill might originate included emergency shut-off valves, bunds and related spill containment structures, and other spill prevention measures. In this case study, a combination of countermeasure options was evaluated to examine the effectiveness of spill mitigation in the Yodo River located in the Kyoto Prefecture of Japan. Results of the case study showed that bunds were emerged as the most useful countermeasure option, reducing the probability of accidents occurring and impact of accidents. We also defined a methodology for calculating the chemical storage volumes appropriate for different countermeasures to ensure that the concentration of chemicals that could reach the water intake does not exceed the standard values. We believe that these methodologies can help chemical-handling companies make decisions when countermeasure options for responding to a chemical spill into a river. Chemical-handling companies can estimate the risk to downstream water treatment plants in the chemical spill, which can also help them consider mitigation measures.