This paper proposes a novel method for site selection of large-scale photovoltaic (PV) power plants using the geographic information system (GIS) and multiple criteria decision making (MCDM). In the proposed method, by consideration of the different constraints and limits such as natural and artificial barriers, the feasible area is decreased in comparison to the whole area. The several important criteria and indices, including solar irradiance, apparent dip, and electrical characteristics are introduced to site selection of PV power plants. The priority and importance of any introduced indices are determined based on experts’ opinions and through using the analytic hierarchy process (AHP). Finally, through the use of techniques for order of preference by similarity to ideal solution (TOPSIS) and the GIS weighed overlay technique, the suitability, and the priority of the different sites regarding PV power plant capabilities are evaluated. Karbala province in Iraq has been selected as an actual cases study. Although, Iraq has a significant capability for PV power plants, but the technical and economic feasibility studies and site selection have not been performed yet. Hence, applying the proposed method to this case study would be interesting and useful based on practical purposes.