This study, focusing on Ghanaian beverage manufacturing firms, investigates the interplay between road transport infrastructure, road safety, and supply chain (SC) performance in emerging economies. Employing a systems theory and knowledge-based views framework, data from 359 managers were analyzed using Partial Least Square-Structural Equation Modeling. Results indicate that road transport infrastructure significantly impacts SC reliability, responsiveness, agility, cost, and asset management. Road safety is a crucial moderator, influencing the relationship between road transport infrastructure and SC reliability, agility, and cost. However, it does not moderate the connection between SC responsiveness and asset management. The study underscores the importance of road safety compliance alongside strategic investments in road infrastructure for improved SC performance in emerging economy manufacturing firms. These findings contribute to innovation literature in the supply chain context, offering practical insights for manufacturing practitioners.