The work aims to explore effects of main chemical mechanical polishing (CMP) process parameters on the material removal rate (MRR) and surface quality of single crystal sapphire substrate and obtain a group of polishing process parameters of high MMR and better surface quality by designing reasonable plans. Atomic force microscope (AFM) and precision balances were used to analyze the morphology and MMR of sapphire substrate respectively. The effects of polishing particle, polishing time, polishing pressure and polishing disk revolution on MRR and surface quality were studied by performing single factor experiments. Proper interactive orthogonal optimal experiments were designed to find a group of optimized process parameters. During the final CMP process of single crystal sapphire substrate, provided with polishing time of 0.5 h, polishing pressure of 45.09 kPa, rotational speeds of 50 r/min, SiO2 slurry particle mass fraction of 15% and polishing slurry flow rate of 60 mL/min, MMR of the sapphire substrate wafer was up to 41.89 nm/min, surface roughness decreased to 0.342 nm and atomic step-terrace structure was clear, meeting the requirements of subsequent epitaxy process. Both high MMR and better surface quality can be obtained at the same time by adopting chemico-mechanical polishing technology and optimal process parameters.