In order to explore the clogging mechanism of filter cakes, a combined approach of prototype experiments and CFD-DEM coupled simulation was used to investigate the variation laws of filter cake thickness and thickness uniformity during the clogging of horizontal screen filters under different conditions. The results show that the cake thickness of the filter is determined by the number of particles in contact with the unit screen area, the flow field force, the inter-particle interaction force and the particle gravity. In the experiments, the filter cake thickness first increases and then decreases with the increase of particle mass concentration, while in the simulations, the filter cake thickness first increases and then stabilizes with the increase of particle mass concentration. Under the same particle mass concentration, the filter cake thickness in both experiments and simulations slowly decreases and then stabilizes with the increase of inlet flow rate. As the particle mass concentration increases, the thickness uniformity of the filter cake first increases and then tends to be stable after reaching the saturation concentration. As the inlet flow rate increases, the thickness uniformity first increases, and then significantly decreases after reaching the critical flow rate. Based on the comprehensive analysis of the thickness and thickness uniformity of the filter cake under various conditions, the operating flow rate of the filter in actual irrigation should not exceed 200 m³/h.