This study focused on the development of the Extended Continental-scale Hydro-economic Optimization model (ECHO) and its application to the analysis of long-term water, energy and land use pathways for Africa. The framework is important because it integrates multi-decadal decisions surrounding investments into new water infrastructure, electric power generation and irrigation technologies. The improved linkages in ECHO reveal synergies between water allocation strategies across sectors and the greenhouse gas emissions resulting from electricity supply. The African case study features a reduced-form transboundary river network and associated environmental flow constraints covering surface and groundwater withdrawals. Interactions between local water constraints and the continental-scale economy are captured in the model through the combination of regional electricity markets. Spatially-explicit analysis of land availability is used to restrict future reservoir expansion. The analysis demonstrates the massive investments required to ensure rapidly expanding water, energy and food demands in Africa aligned with human development objectives are met in a sustainable way. Modeled constraints on environmental flows in line with presumptive ecological guidelines trigger diffusion of energy-intensive water supply technologies in water-stressed regions, with implications for the cost and speed of the electricity sector decarbonization required to achieve climate targets.