The study examined the mediating role of supply chain security performance on the relationship between supply chain security practices and supply chain disruptions occurrences in the manufacturing industry in Ghana. Drawing on a survey of 336 manufacturing firms, dynamic capability, and contingency theories were applied using structural equation modeling (SEM) to test the conceptual model. It was discovered that both direct and indirect hypotheses supported the findings of the study. The results indicate that Ghanaian manufacturing firms have made progress in implementing supply chain security measures. The findings revealed that the adoption of comprehensive supply chain security practices is positively associated with improved performance metrics, including reduced inventory losses and damages, faster order fulfillment and delivery times, lower costs related to security incidents, and enhanced brand reputation and customer trust. Policymakers can leverage these insights to develop support programs aimed at strengthening the security capabilities of manufacturing firms, ensuring they are equipped to compete effectively in both local and global markets, improving security performance, and reducing the likelihood and impact of supply chain disruptions. In the quest of bridging the gap between theory and practice, this research contributes valuable knowledge to the discourse on supply chain security in developing countries, offering a roadmap for enhancing resilience and performance in the manufacturing sector.