In this study, we examined the influence of the organic carbon-to-nitrogen ratio (chemical oxygen demand (COD/N)) and dissolved oxygen (DO) levels on the removal efficiency of pollutants and on the change in total microflora in the cyclic activated sludge system (CASS) in the Nyingchi prefecture in Tibet. The results demonstrated that the treatment performance was the best when the COD/N ratio was 7:1 or the DO levels were 2–2.5 mg/L in comparison with four different tested COD/N ratios (4:1, 5:1, 7:1, and 10:1) and DO concentrations (0.5–1, 1–2, 2–2.5, and 2.5–3.5 mg/L). The treatment performance can be explained by the relative operational taxonomic unit richness and evenness of the microbial communities in activated sludge. Evident microbial variance was observed, especially different COD/N ratios and DO concentrations, which were conducive to the disposal of urban sewage in plateaus. The results help to understand sewage treatment under different COD/N ratios or DO concentrations on plateaus. This work provides practical guidance for the operation of any wastewater treatment plant on a plateau.