Due to rapid industrialization of agriculture, increased global food demand, and, increasing concerns related to food quality and safety, the concept of sustainability and supply chain transparency are becoming critically important to the agriculture and agri-food sector. The addition of sustainability performance objectives not only focuses on the effective utilization and consumption of natural resources, but also drives efforts to balance ecological, economic and societal aspects of agri-food businesses. The management of sustainability adds a new demand on business managers who often have small profits and receive stringent requirements from large powerful customers and retailers. In this paper, we recognize and analyze the key enablers in implementing sustainable initiatives for Agri-Food Supply Chains (A-FSCs). Ten important sustainability driven enablers were considered from a rigorous literature review and phase of expert consultation. The identified enablers were then analyzed using a combined Interpretive Structural Modeling (ISM)-fuzzy Decision Making Trial and Evaluation Laboratory (DEMATEL) based framework. The ISM approach enabled an appreciation of the contextual relationships among the enablers and to classify the enablers based on their driving and dependence potential. The fuzzy DEMATEL technique supported the determination of the influential and influenced enablers and also to categorize them into cause and effect groups. An empirical case study, drawn from a vegetable and fruit retail supply chain in India, is used to focus and test the applicability of the proposed research framework. The paper facilitates professional management practice and researchers to uncover and explore the enablers for the real execution of sustainability oriented initiatives in the agri-food business sector.