Ozonation is a commonly used method to enhance coagulation during reclaimed water treatment, which can significantly reduce the formation of disinfection byproducts (DBPs) due to the removal of dissolved organic matter. However, effects of different combination sequences and operation conditions of ozonation-enhanced coagulation on effluent organic matter (EfOM), especially dissolved organic nitrogen (DON), as well as the subsequent DBP formation and toxicity are not well investigated. In this study, the coagulation effects of polyaluminum chloride (PAC) and polyferric sulfate (PFS), as well as the optimal coagulation conditions were determined. The effects of the ozone dose and combination sequence of ozonation-enhanced coagulation on EfOM properties, DBPs, and acute toxicity were investigated. The results showed that the optimal coagulation conditions were achieved by PFS at a dose of 80 mg/L, and removal efficiencies of dissolved organic carbon (DOC), DON, and acute toxicity were 36%, 40%, and 21%, respectively. For ozonation-enhanced coagulation, the optimal removal efficiencies were achieved at a 1 mg/L ozone dose. Among the three combination sequences, the hybrid ozonation-coagulation process had the highest removal efficiencies for DON (43.8%), carbonaceous DBPs (34.5%), nitrogenous DBPs (33.8%), and total organic halogen (38.0%), respectively. For DOC and acute toxicity, the highest removal efficiencies were achieved by the post-ozonation process (20.9%) and pre-ozonation process (16.4%), respectively. The formation of center dot OH and the increasing Fec content led to the enhancement of the hybrid ozonation-coagulation process, and the decreasing Feb content led to the negative impact on the removal of DOC by the hybrid ozonation-coagulation process.