Iran is the main watermelon producer in the world after China and Turkey. However, there is no practical information on which region, tillage and cultivation systems can achieve the most efficient watermelon production system in Iran. This study was conducted to assess the most efficient ways of watermelon production in three agroecosystems (cold, moderate, warm) of Iran using Data Envelopment Analysis. The data were collected from two tillage systems (reduced and conventional) and two groups of watermelon cultivations (conventional system and plastic film mulching system). Accordingly, twelve watermelon production systems were under the study including all inputs and outputs. Finally, an Analytical Hierarchy Process model was used to determine the best region and the best combination of cultivation and tillage systems for watermelon production. The technical and pure technical efficiencies of watermelon production systems were respectively 89%–100%. The Analytical Hierarchy Process model determined that the most efficient watermelon production systems were from combination of plastic film mulching system and reduced tillage in cold and moderate agroecosystem which reduced water and diesel fuel consumption by 500–2500 m3/ha followed by fertilizers by 100–150 kg/ha while efficiencies are enhanced by 20%–32%.