N-nitrosamines (NAs), a class of emerging nitrogenous disinfection byproducts, have been detected remarkably in drinking/reclaimed water. There is a significant risk of excessive levels of NAs in the chlorination of the polluted source water, especially in the direct chlorination of nitrite-enriched groundwater. Considering the co-pollution of nitrite and micro-organic pollutants on groundwater, experiments were conducted on chlorination of nitrite-enriched water with precursor of antibiotics, and it was confirmed that the Cl2: N (molar ratio of chlorine to nitrite), contacting time, pH, and DO appreciably influenced the NAs formation potential. The molecular electric potential revealed that different dissociation status of precursors has a specific correlation with NAs formation potential (FP). The nitrite significantly increased the NAs FP because the reactive nitrogen species (RNS) formed in the oxidation process from nitrite to nitrate. Sequences of transformation products are determined to support the RNS promoted hypothesis of N-nitrosodimethylamine (NDMA) formation mechanism; furthermore, theoretical investigation in the reaction of dimethylamine (DMA) with different RNS verified the above hypothesis. Display omitted •NDMA FP significantly promoted in chlorination of nitrite-enriched groundwater.•DO is not a key factor to NDMA formation in nitrite-enriched situation.•RNS enhanced-nitrosation pathway was proposed.•NDEA has been detected along with NDMA formation.