Titanium alloys require excellent surface quality to achieve superior performance in biomedicine. In this paper, chemical mechanical polishing (CMP) was employed to prepare a satisfactory TC4 alloy surface. F− and persulfate were used as critical additives to improve the CMP efficiency. In comparison with the basic slurry without F− and persulfate, the slurry containing only F−, and the slurry containing only persulfate, the slurries containing both F− and persulfate lead to a noticeable increase in the material removal rate (MRR), which is attributed to the synergistic effect of F− and persulfate. After adding 80 mM NaF and 100 mM (NH4)2S2O8 to the basic slurry, the MRR increases significantly from 11 nm min−1 to 203 nm min−1, and the surface roughness R
a
reaches 3.4 nm. Moreover, there is no processing damage in the substrate. For the synergistic effect, Ti in TC4 alloy is first oxidized to Ti3+ and Ti4+ oxides by persulfate, and then HF, F− and HF2
− attack the oxides to produce soluble complex compounds, promoting the corrosion and the resultant MRR. This study provides a feasible way to achieve the high-efficiency CMP of titanium alloys via the synergistic effect of complexing agent and oxidizer to enhance the corrosive wear.