Purpose: This study investigates the relationship between organizational security culture and supply chain disruptions, and examines the mediating role of supply chain security practices in mitigating disruptions. Methodology: A quantitative approach was employed, surveying 350 managers from Ghana's manufacturing and service sectors. Structural Equation Modeling (SEM) analyzed the relationships between organizational security culture, supply chain security practices (information management security, facility management security, and human resource security), and supply chain disruptions. Results: The study reveals that a robust organizational security culture has a profound impact on supply chain security practices, resulting in a substantial reduction in supply chain disruptions. Specifically, facility management security and information management security emerge as critical mediators, significantly influencing this relationship. Conversely, human resource security does not have a statistically significant impact. Conclusion: This study contributes to the supply chain security management literature, highlighting the importance of organizational security culture in mitigating supply chain disruptions. The findings provide valuable insights for managers and policymakers seeking to enhance supply chain resilience in emerging economies. The study emphasizes the need to integrate organizational security culture and supply chain security practices. Managers should prioritize building a strong security culture, allocate resources for effective supply chain security practices, and promote employee awareness.