Groundwater resources are essential for the supply of drinking water in the European Union but significant uncertainties surround their quality. In this context, our article analyzes the factors that influence the cooperation of key stakeholders to prevent the risk of diffuse pollution from agriculture. We built on the institutional rational choice approach and the social-ecological system framework to design our analytical framework and hypotheses. We applied this analytical framework to two cases of cooperation involving drinking water suppliers and farmers in the management of the risk of non-point source pollution from agriculture in France. Our results show that cooperation emerges when the water resource is important for water suppliers to take on the leadership. Our results also characterize the role played by uncertainties and risk in getting stakeholders involved, and finally, suggest that cooperation depends on the size and predictability of the resource system.