A fire risk analysis was conducted to evaluate and manage the potential for accidents in the petrochemical industry. From the perspective of systems and control theory, this study proposes a fire risk assessment and management method for chemical plants based on system-theory accident models and processes. An integrated framework was proposed to assess and manage fire risk in chemical plants. Hazard and operability analyses were conducted to identify the deviations and contributing factors leading to fires in a chemical plant. For fire risk points, a hierarchical control structure model of the system production process was integrated with the internal production and external safety management interactive feedback unit to clarify the safety constraints and controls. Chemical plant operation scenarios were developed to focus on coordination and feedback between multiple organizations in the system. A decision-making trial and evaluation laboratory (DEMATEL) and interpretative structural modeling (ISM) were combined with an analysis of constraint defects. A case study of a fatty alcohol polyoxyethylene ether plant was conducted. The results show that the DEMATEL–ISM model describes the potential cross-level control process and can comprehensively analyze the relationship between contributing factors to improve the system’s overall safety and prevent accidents.