Due to its synergistic effects, sequential disinfection is considered a viable treatment option for the effective inactivation of pathogenic microorganisms that cannot be treated using the single-step application of chlorine-based disinfectants. This study systematically demonstrated the applicability of sequential disinfection with chlorine dioxide followed by chlorine to control disinfection byproducts. At pH 7,chlorine dioxide/chlorine treatment suppressed the formation of trihalomethanes (THMs) by 10.0% and 25.0% at temperatures of 10℃ and 20℃, respectively, compared to chlorine only. In addition, when using chlorine oxide/chlorine disinfection, a higher pH led to amore significant suppression of THMs production. It was also found that THMs production was lower as the chlorine dioxide dosage increased; in particular, the use of 1.2 mg/L and 5.0 mg/L chlorine dioxide at pH 9 had a substantial suppressive effect on THMs formation, with a reduction of 25.8% compared to chlorine only. Higher temperatures and a higher dissolved organic carbon concentration suppressed the generation of THMs in the chlorine dioxide/chlorine disinfection system compared with the chlorination alone.