Water reclamation plants (WRPs) are facing the challenges of ensuring microbial safety and require efficient disinfection systems. Sequential ozone‑chlorine disinfection is supposed to be a favorable alternative for reclaimed water disinfection. This study compared the inactivation efficiency of E.coli by single ozone, single chlorine, and sequential ozone‑chlorine disinfection approaches. Notably, a single ozone or chlorine process could only achieve a log removal rate of up to 5 log, whereas the sequential ozone‑chlorine disinfection could completely inactivate microorganisms (7.3 log). For sequential ozone‑chlorine disinfection, the efficiency of chlorination was improved by 2.4%-18.5%. The synergistic effect mainly attributed to the elimination of chlorine consuming substances by ozone. Through the chlorine decay model (CRS) fitting and calculating the integral CT value, the enhancement ability of ozone to chlorine disinfection was quantified. By introducing an enhancement coefficient (β), a succinct and accurate model was established to estimate the inactivation rate of sequential ozone‑chlorine disinfection (mean absolute percentage error: 0.035). The results and methodology of this study are informative to optimize the disinfection units of WRPs.