Many public transport authorities have a great interest in introducing zero-emission electric buses. However, the transformation process from diesel to electric bus systems opens up a vast design space which seems prohibitive for a systematic decision making process. We present a holistic design methodology to identify the ‘most suitable system solution’ under given strategic and operational requirements. The relevant vehicle technologies and charging systems are analysed and structured using a morphological matrix. A modular simulation model is introduced which takes technical and operational aspects into account. The model can be used to determine a feasible electric bus system. The technology selection is based on a detailed economic analysis which is conducted by means of a total cost of ownership (TCO) model. To cope with uncertainties in forecasting, a stochastic modelling of critical input parameters is applied and three different future scenarios are evaluated. The applicability of the model was verified in a pilot project in Berlin and the methodology was applied to a realistic operational scenario. Our results indicate that electric bus systems are technically feasible and can become economically competitive from the year 2025 under the conditions examined.