The ubiquity of antibiotic-resistance bacteria (ARB) and antibiotic-resistance genes (ARGs) in various environmental matrices is a potential threat to human and ecological health. Therefore, the inactivation of ARB E. coli S1-23 and the elimination of its associated ARGs, blaTEM-1 and aac(3)-II, were investigated using the photoelectrocatalytic (PEC) process. Results indicate that the ARB E. coli S1-23 (1 × 108 cfu mL−1) and its ARGs (extracellular and intracellular) could be fully inactivated within 10 and 16 h PEC treatment, respectively. In contrast, photocatalytic (PC) and electrochemical (EC) treatments displayed no obvious effect; however, ARG-containing DNA extracted from E. coli S1-23, which was used as a model for dissociative naked ARGs, could be completely decomposed within a few minutes through these three treatments. Further analyses, including PCR, AFM and HPLC, proved that the structural integrity and surface topography of naked ARGs are damaged during treatment and can be completely eliminated. Furthermore, there is no generation of cytosine, guanine, adenine or thymine intermediates during the PEC, PC, and EC treatments. This study is the first report to propose the PEC treatment as a promising method for complete decomposition of ARB and ARGs in aqueous systems.