Virtual sensing is crucial in order to provide feasible and economical alternatives when physical measuring instruments are not available. Developing model-based virtual sensors to calculate real-time information at each targeted location is a complex endeavor in terms of sensing technology. This paper proposes a new approach for model-based virtual sensor development using computational fluid dynamics (CFD) and control. Its main objective is to develop a three-dimensional (3D) real-time simulator using virtual sensors to monitor the temperature in a greenhouse. To conduct this study, a small-scale greenhouse was designed, modeled, and fabricated. The controller was based on the convection heat transfer equation under specific assumptions and conditions. To determine the temperature distribution in the greenhouse, a CFD analysis was conducted. Only one well-calibrated and controlled physical sensor (temperature reference) was enough for the CFD analysis. After processing the result that was obtained from the real sensor output, each virtual sensor had learned the associative transfer function that estimated the output from given input data, resulting in a 3D real-time simulator. This study has demonstrated, for the first time, that CFD analysis and a control strategy can be combined to obtain system models for monitoring the temperature in greenhouses. These findings suggest that, generally, virtual sensing can be applied in large greenhouses for monitoring the temperature using a 3D real-time simulator.