Applying John R. Commons institutional economic framework, this paper analyzes the evolution of the key institutions in the Malian cotton sector starting with the CFDT contract following the country‘s Independence in 1960; the nationalization of the cotton gin company, CMDT, in 1974; the completion of a vertically integrated market structure from the mid-1980s to mid-1990s; and, finally, to the current state of the market-oriented reforms in 2010. In accordance with John R. Commons’ economic theory, institutional changes in the Malian cotton sector have led to both intended and unintended consequences impacting economic performance at the farm, gin, and State levels, which in turn, has contributed to the emergence of new limiting factors. At present, the limiting factors to desired economic performance in the Malian cotton sector are: the lack of adequate extension services, high rates of indebtedness at both farmer and cooperative levels, difficulty in farming in an integrated system due to the limited access to cereal inputs on credit, low yields, delays in payment, and discordance between farmers and their union‘s leaders. Based on these findings, policy recommendations to revitalize the Malian cotton sector are drawn.