Vast quantities of by-products, perceived as waste, are created along the supply chain in agro-food systems. To mitigate this, studies recommend firm-level environmental management and industrial symbiosis (IS), where material and energy flows are circulated within and among industries to minimise waste. This research employed the mixed method approach, applying input–output and material flow analyses to investigate by-product reuse and interdependency (existing synergies) within and among enterprises, and modelled an Eco-Industrial Network (EIN) for potential synergies among enterprises within the agro-food value chain in Ghana using Stan2web, a material flow analysis tool. Results showed that, although 88% of enterprises had knowledge of interdependencies, only 78.86% of them implemented environmental management at the firm level, with 53.84% of firms engaged in exchange of material across enterprises. The noticeable existing synergy was between the food and non-alcoholic beverage industries, and the waste management industry, for the manufacture of compost. Modelling potential synergies, the study revealed that establishing wastewater treatment and steam and/or biogas plants in addition to incentives from regulators would be essential to transitioning towards circularity. This study recommends further education in Industrial Ecology (IE) to create opportunities to enhance interdependencies among firms.