A combined heterotrophic-sulfur-autotrophic system (CHSAS) was established to simultaneously reduce perchlorate and nitrate in water. In this system, the OH produced by the acetate heterotrophic part (H-part) could be neutralized with the H produced by the sulfur autotrophic part (S-part); thus, the pH of the final effluent could keep neutral. In addition, the S-part could further reduce the pollutants and residual carbon from the H-part to achieve a high performance. For 19.62 ± 0.30 mg/L ClO and 21.56 ± 0.83 mg/L NO-N in the influent, the operating parameters were optimal at a hydraulic retention time (HRT) of 1.0 h and an acetate concentration of 70 mg/L. The removal efficiency of ClO and NO reached 95.43% and 99.23%, without secondary pollution caused by residual organic carbon. It was also revealed that sulfur (S) disproportionation can be inhibited by shortening the HRT and reducing the acetate dosage. The dominant heterotrophic and autotrophic bacteria were Thauera and Ferritrophicum, respectively, while Chlorobaculum was related to S disproportionation.