As a crucial substrate material for optoelectronic materials, sapphire has important applications in both military and civilian fields. In order to achieve the final processing quality of sapphire substrate materials, double-sided chemical mechanical polishing (DS-CMP) is a necessary process, which is also a guarantee for the preparation of high-end LED chips. Here, the sapphire DS-CMP processing plan based on the Box-Behnken design is obtained and experimented, then a hybrid approach of response surface method (RSM) and support vector machines (SVM) algorithm is established as the material removal rate (MRR) prediction model for sapphire DS-CMP. Furthermore, the material removal process of sapphire DS-CMP, the influence of response variables on the MRR of sapphire DS-CMP, and the prediction results of RSM-SVM on sapphire DS-CMP are analyzed respectively. From the experimental results, the maximum MRR obtained is 387.59 nm/min, which is more than six times the reported MRR of single-sided CMP under similar process parameters. The mean square error of predicted value through RSM-SVM is basically around ±10% of the experimental value, which possess satisfied validity for the MRR prediction of sapphire DS-CMP. Finally, both top and bottom surface quality of sapphire wafers after DS-CMP processing was investigated.