This study presents the effective performance of a sustainable solar driven agricultural greenhouse (GH) self-reliant of energy and irrigation water via desalination. The GH is furnished with infrastructures such as; (i) - an inlet condenser for cool air exchanger and partial water production, (ii) - an internal cavity for crop production (iii) - roof transparent solar distillers (TSD) for solar desalination and partial shading and (iv)- a thermal chimney for natural air ventilation. A mathematical model is developed to predict the performance of the sustainable GH system. A coupled approach of MATLAB/Simulink and computational fluid dynamics (CFD) based on three simulation models were used: solar radiation, thermal energy balance and CFD model. Two parametric studies were carried out. The first one analyzed the effects of different air velocity on the system thermal performance and natural ventilation rate. The second study assessed the effects of different covering material on the transmitted solar radiation. Results from the model shows that 8.5 MJ/m2.day of total solar radiation is transmitted into the GH. The greenhouse air temperature is lowered by 5 °C and humidified by 20%, to satisfy the required conditions necessary for plant growth. Maximum water yield of 11.5 L/m2.day was obtained, aided by the addition of Al-metal net. Additionally, 2.6 kWh/m2.day of power is consumed by the air-cooling condenser. At air velocity of 0.3 m/s, there is a natural tendency of air to flow by draft, due to air temperature difference of up to 4 °C. Furthermore, glass and EVA cover materials transmit 52 and 48% of solar radiation into the GH respectively. The proposed system will enable the parallel production of water and food and enhance economical plant productivity.