Chlorine disinfection has become the most widely applied and indispensable technology in wastewater treatment and reuse to mitigate microbial risk and guarantee water safety. However, owing to complexities and high concentrations of contaminants in reclaimed water, rapid evaluation of chlorine disinfection efficacy is a crucial but challenging issue. Based on intensive experimental and statistical analyses, this study has established kinetic models and potential surrogates for rapid indication of the inactivation of microbial indicators and opportunistic pathogens during chlorine disinfection in different reclaimed waters. Overall, the constructed Selleck models performed very well to simulate log removal values (LRVs) of fecal coliforms, Pseudomonas aeruginosa and heterotrophic plate counts in all reclaimed water samples (R2 = 0.877–0.990). Moreover, total and Peak A fluorescence intensity as well as fluorescence integral intensities in Regions II and IV were found to have high response sensitivities during the chlorination process. Nevertheless, their effectiveness to act as potential surrogates of LRVs of microbial indicators needs to be further validated. The results from this study can provide valuable information on microbial safety surveillance of disinfection toward sustainable and long-term water reuse.