Despite of a high abundance of antibiotics, heavy metals, and organic matters detected in the Saigon River in Ho Chi Minh City, the level and spread of antibiotic resistance genes in this river are poorly understood. In this study, total 10 antibiotic resistance genes (ARGs), including genes conferring resistance to aminoglycosides (aac(6)-Ib-cr), β-lactam antibiotics (blaCTX-M, blaSHV, blaTEM), quinolones (qnrA, qnrB), sulfonamides (sul1, sul2), trimethoprim (dfrA), efflux pump (oqxB), and three genes of genetic elements, including integron classes 1, 2, and 3 (intI1, intI2, intI3), are quantified by qPCR. Water samples were collected from the industrial, agricultural, residential, and less impacted areas for the wet and dry seasons. The results present high occurrence rates for 10 ARGs that were observed in all the sampling sites with the following order: sul1, sul2, dfrA > aac(6)-Ib-cr > blaCTX-M, blaSHV, blaTEM > qnrA, qnrB. Although the levels of ARGs and integrons in the dry season were found about to be about one order of magnitude higher than those in the wet season, the exact mechanisms for this are not fully clear. The correlation analysis presented here suggests that the contamination of organic matter and nutrients from agricultural, industrial, and residential activities likely contributes to the prevalence of ARGs, integrons, total bacterial load, and the potential development and spread of antibiotic resistance in the aquatic environments considered here.