The distribution of antibiotic resistance genes (ARGs) in Laizhou Bay affects the local socio-economic development. The study aimed to investigate the distribution of ARGs in the rivers that flow into the sea around Laizhou Bay’s southern shore. Water and sediment samples were collected from different typical sites of rivers entering the sea in Weifang, including Mi River, Bai Lang River, Yu River, Wei River, Jiaolai River, Xiaoqing River and Di River. The species and abundance of ARGs in the sediments were characterized and quantified by macro-genome high-throughput sequencing technology. The species distribution of ARGs was compared. In two sediment samples and seven water samples, 24 ARGs types and 1244 subtypes of ARGs were detected, in which multidrug-resistant class was the main ARGs type and FBJ murine osteosarcoma viral oncogene homolog B (fosB) was the dominant ARGs. The types of ARG in the top ten of these samples were the same, although the proportion was different. Dominant ARG subtypes accounted for more than 50% of all the nine samples. This article provides basic data support for pollution status and environmental risk assessment as well as remediation of ARGs in rivers entering the sea along the south coast of Laizhou Bay.