High-throughput sequencing was applied to analyze correlations among environmental factors, antibiotic resistance genes(ARGs), mobile genetic elements(MGEs) and microbial communities in the Yuan River, so as to explore distribution patterns, primary driving factors and potential host characteristics of ARGs in the river. The results showed that sulfamethoxazole and roxithromycin were dominant antibiotic contaminants in the Yuan River. A total of 159 ARG subtypes belonging to 14 classes were detected across all water samples，among which aminoglycoside and multidrug resistance genes possessed higher average relative abundances, and multidrug efflux pump gene mdtG exhibited the highest average relative abundance of 0.455 (normalized to 16S rRNA gene). Both total antibiotic concentrations and total relative abundances of ARGs were higher in downstream reaches than upstream reaches. Mantel test revealed no significant direct correlations between ARGs and most environmental factors, nor between MGEs and environmental parameters. Significant positive correlations were observed among environmental factors, ARGs and most dominant microbial taxa, implying that environmental factors (including residual antibiotics) indirectly regulate distribution of ARGs by altering composition of dominant microbiota. Two taxa, unclassified_f_Bacteroidetes_vadinHA17 and unclassified_o_Vicinamibacterales, were predominant in the Yuan River and served as primary potential hosts of detected ARGs throughout the watershed.