The high levels of 16 detected ARGs were demonstrated in Xiangjiang River. The ARGs released from the PWWTP is a major source in the upstream of Xiangjiang River. Selective stress of heavy metals significantly influenced the distinct distribution pattern of ARGs in the downstream. Individual ARG subtypes were correlated with heavy metal resistance genes. Heavy metals act as the stressors co-selected the ARGs in the same plasmid of antibiotic resistant bacteria.