Greenhouses are closed environments that require careful climatic control, which can benefit from a system control method to cope with the high nonlinearity, complex coupling, and robustness of unknown disturbances. This paper presents a general framework for an integral sliding mode controller based on a disturbance observer combined with feedback linearization for a greenhouse temperature and humidity system. The first-principle greenhouse climate model is described as a standard affine nonlinear system. The feedback linearization control law is used to achieve a system consisting of two separate integrator channels for temperature and humidity. System compound disturbances are estimated by applying a sliding mode disturbance observer. Based on the observer, an integral sliding mode control is incorporated to enhance the robustness against uncertainties and guarantee satisfactory tracking performance even when there are unknown estimation errors. The validity and efficacy of the proposed control technique for greenhouse climate tracking were verified by comparison with simulation results obtained using the common sliding mode control method using feedback linearization without the disturbance observer. Based on this comparison, the developed controller shows a faster system response speed, higher control precision, and stronger anti-interference ability. This method can be applied to improve greenhouse climate control systems.