Abstract Global environmental change is driven by food production. Biogas from food waste is a better source of clean energy. Ghana’s energy strategy targets a 10% increase in renewable energy and modern biomass in the national electricity generation mix. Studies on the assessment of electricity generation potential and economic feasibility of biogas to electricity projects in Ghana’s major cities are scarcely available. This study assesses the electricity generation potential of biogas from food waste through anaerobic digestion technology. The municipal solid waste generation potential of Accra and Kumasi was estimated from 2020 to 2039. The potential theoretical methane yield from food waste was calculated using Buswell’s equation. The study analyzed anaerobic digestion projects’ economic feasibility using the total life cycle cost, net present value, investment payback period, levelized cost of energy, and internal rate of return methods. A sensitivity analysis based on two scenarios (optimistic and pessimistic) was performed to analyze the influence of changes in the composition of food waste, per capita waste generation rate, population growth rate, per capita GDP growth rate, discount rate, capacity factor, electricity generation efficiency, waste collection efficiency, and methane production potential on the economic feasibility of the projects. The main findings indicate that the amount of waste generation in Accra during the project life cycle is 899,000 t/y to 3,359,000 t/y, while that of Kumasi is 915,000 t/y to 3,159,000 t/y. The power generation potential of the project in Accra ranges from 80.43 to 300.49 GWh/y, and in Kumasi ranges from 60.63 to 209.31 GWh/y. Economically, the project is feasible in Accra and Kumasi. The net present value of the project in Accra and Kumasi is $217,800,000 and $156,100,000. The sensitivity analysis shows that the project is infeasible in all the cities with a discount rate exceeding 20%. When the discount rate exceeds 20%, the project becomes highly infeasible in Accra compared to Kumasi. This study will offer itself as scientific guidance for investment in biogas to electricity projects in Ghana’s cities.