Iron slag, a byproduct of the wet zinc refining process, contains a substantial amount of valuable metals such as iron and zinc, making it highly valuable for comprehensive recovery and reuse. However, before recovery, the iron slag requires dehydration pretreatment. The water content in iron slag remains relatively high and difficult to remove even after pressure filtration, leading to extended drying times, reduced drying efficiency, and increased energy consumption. This study explores a novel ultrasonic pretreatment process for iron slag. Using the response surface methodology, we investigated the effects of ultrasonic power, ultrasonic time, liquid-to-solid ratio, and their interactions on the water content, capillary suction time (CST), and filtration resistance of the slag. Regression equations were established to predict the relationships between the water content, CST, filtration resistance, and the various factors. The optimal process parameters were determined as an ultrasonic power of 60 W, ultrasonic time of 22 s, and a liquid-to-solid ratio of 4:1. Under these conditions, the dehydration performance of the iron slag was optimal. The measured values closely matched the predicted values, demonstrating the reliability of the model and the feasibility of the optimized process. Our study of the mechanism of ultrasonic action on iron slag found that under the influence of ultrasonic waves, the particle size of the slag significantly decreased, and the particle morphology changed. Compared to conventional drying, the drying rate of the iron slag after ultrasonic pretreatment was accelerated, and the drying time was reduced.