Antibiotic resistance is a serious public health risk that may spread via potable and reclaimed water. Effective disinfection is important for inactivation of antibiotic-resistant bacteria and disruption of antibiotic resistance genes. Ampicillin is a widely prescribed antibiotic but its effectiveness is increasingly undermined by resistance. In this study, changes in ampicillin resistance for Escherichia coli (E. coli) CGMCC 1.1595 were analyzed after exposure to different doses of ultraviolet (UV) or chlorine, and damage incurred by the plasmid encoding ampicillin resistance gene bla_TEM-1 was assessed. We reported a greater stability in ampicillin-resistant E. coli CGMCC 1.1595 after UV irradiation or chlorination when compared with previously published data for other E. coli strains. UV irradiation and chlorination led to a shift in the mortality frequency distributions of ampicillin-resistant E. coli when subsequently exposed to ampicillin. The ampicillin hemi-inhibitory concentration (IC₅₀) without disinfection was 3800 mg·L^-1, and an increment was observed after UV irradiation or chlorination. The IC₅₀ of ampicillin-resistant E. coli was 1.5-fold higher at a UV dose of 40 mJ·cm^-2, and was 1.4-fold higher when exposed to 2.0 mg·L^-1 chlorine. These results indicate that UV irradiation and chlorination can potentially increase the risk of selection for E. coli strains with high ampicillin resistance. There was no evident damage to bla_TEM-1 after 1–10 mg Cl₂·L^-1 chlorination, while a UV dose of 80 mJ·cm^-2 yielded a damage ratio for bla_TEM-1 of approximately 1.2-log. Therefore, high UV doses are required for effective disruption of antibiotic resistance genes in bacteria.