Abstract Tea polyphenols can be developed into new types of disinfectants for drinking water. The antibacterial effect of epigallocatechin gallate (EGCG) on Escherichia coli (E. coli) in the presence of Ca2+ is affected by the Ca2+ concentration. The oxidative damage mechanism and oxidative damage process of EGCG in E. coli under the presence of Ca2+ were deeply analyzed under three aspects: reactive oxygen species (ROS), antioxidant system, and oxidative stress response in E. coli to provide a theoretical basis for the use of EGCG as a disinfectant in drinking water disinfection. EGCG leads to excessive production of superoxide anion in E. coli and the presence of Ca2+ promotes further imbalance of superoxide anion in E. coli; Ca2+ has little effect on EGCG hindering the scavenging of hydroxyl radicals in bacteria; EGCG can hinder the effect of antioxidant enzymes in E. coli, and Ca2+ has a particular regulatory effect on antioxidant enzymes, thus hindering the oxidative damage of EGCG to E. coli; Ca2+ can cause the expression of the oxyR and DPS genes, protect bacterial DNA, and prevent EGCG from damaging bacterial DNA. In the presence of a high concentration of Ca2+, it may activate the cell efflux pump through the soxS gene, resulting in E. coli resistance to EGCG.