This study investigates the effect of chemical mechanical planarization (CMP) processing parameters such as platen velocity, concentration of the oxidizer and abrasive nanoparticle, slurry pH, and surfactant types on the surface roughness of cadmium zinc telluride (CdZnTe) substrate. It was found that these parameters have a significant effect on the quality of the polished surfaces. It was also found that lower platen velocity, lesser abrasive particles concentration, basic slurry pH, and addition of anionic surfactant into the CMP slurry solution improved surface planarity. Optical surface profiler and atomic force microscopy techniques were used to monitor the surface topography before and after polishing. A notable root-mean-square surface roughness, (Rq), ~0.9 nm, has been obtained on polished CdZnTe (CZT) surface over a scan area of 481×361 µm2 under the optimized conditions of 60 rpm relative velocity, slurry pH of 9, 3.75 vol. % of oxidizer (H2O2) and 1.25 wt. % of abrasive (SiO2 nanoparticle). A probable mechanism of the present CMP surface planarization of CZT substrate has been proposed. Unlike the conventional surface planarization processes, which involve two-step lapping followed by CMP for the CZT surfaces, we have developed a single step CMP process to obtain good surface planarity.