Although domestic wastewater is a reservoir of antibiotic resistance factors including antibiotic resistant bacteria, genes, and many other pollutants including antimicrobial compounds, most of the current treatment processes in the wastewater treatment plant (WWTP) are not designed to specifically remove these emerging contaminants. In this study, the occurrences and removal efficiency of antibiotic resistant Escherichia coli and genes in a WWTP were examined, and explored any potential correlations between these antibiotic resistance factors and physicochemical parameters, nutrients, and heavy metal levels in wastewater. Wastewater samples were collected at five sampling sites after different treatment processes in a WWTP in Ho Chi Minh City, Vietnam. The concentrations of E. coli resistant to amoxicillin/clavulanic acid, amikacin, cefixime, ciprofloxacin, and sulfamethoxazole/trimethoprim were determined using Tryptone Bile X-glucuronide agar supplemented with target antibiotics and then confirmed with indole test. The levels of the total bacterial 16S rDNA, integron integrase genes (intI1, intI2, and intI3), efflux pump (OqxB), and antibiotic resistance genes (sul1, sul2, dfrA, aac(6)-Ib-cr, qnrA, qnrB, blaTEM, and blaCTX) were quantified using qPCR assay. As the results, the concentrations of E. coli resistant to the five tested antibiotics in wastewater influent were ranging from 32.7 to 1.8 × 104 CFU/mL, and resistance rates to AMC, CEF, SXT, CIP, and AMK were 78.9, 43.0, 25.0, 24.0, and 0.1%, respectively. Among tested genes, the sul1, sul2, intI1, and aac(6)-Ib-cr were highly detected in the influent wastewaters with the average concentrations ranging from 1.29 × 106 to 1.09 × 108 GCN/mL, followed by qnrA, OxqB, intI3, dfrA, and blaTEM with the average concentrations ranging from 6.32 × 104 to 1.26 × 105 GCN/mL, and qnrB, intI2, and blaCTX detected at the low levels ranging from 1.43 × 103 to 1.61 × 104 GCN/mL. Although overall removal efficiencies of antibiotic resistant E. coli and genes for the final effluent were up to 99.9%, the detectable levels of ARB and ARGs in the final effluent were still of concern as these emerging contaminants can be discharged into the environments. © 2023, The Author(s) under exclusive licence to Iranian Society of Environmentalists (IRSEN) and Science and Research Branch, Islamic Azad University.