Erosional damage to sand control screens from sand-laden fluids is a critical issue affecting well integrity and service life. Existing research has predominantly focused on screen plugging conditions, while the erosion mechanism under unplugged conditions remains poorly understood. Laboratory experiments, numerical simulation, and a multiple regression model was integrated to systematically deconstruct the effects of flow velocity, particle size, and sand flow rate on screen erosion. The experimental results indicate that screen mass loss increases with all three factors, with the influence of flow velocity being the most significant and exhibiting an accelerating trend. Numerical simulations revealed that erosion is concentrated in narrow flow passages, such as screen slots, which suffer severe scouring due to localized flow acceleration. The regression analysis quantified the contribution of each factor: flow velocity had the highest impact at 56.1%, followed by sand flow rate at 35.7%, and particle size having the lowest at 8.2%. The study confirms that flow velocity is the primary controlling factor for erosion in unplugged screens and should be given special consideration in sand control operations. The findings provide an experimental basis and theoretical reference for the optimization of sand control measures and screen structural design.