<p>Antibiotic resistance genes (ARGs), as emerging environmental pollutants, pose a significant threat to global public health and offshore ecological safety through their environmental fate and dispersion mechanisms. To comparatively assess the differential impacts of distinct anthropogenic activities (<i>e.g.</i>, concentrated industrial vs. diffuse agricultural runoff) on ARGs in estuaries, we selected the estuarine sediments of two urban rivers (Baisha River, BSH and Licun River, LCH) and two rural rivers (Dagu River, DGH and Yang River, YR) in Jiaozhou Bay, and systematically analyzed the urban-rural distribution differences of ARGs and their driving mechanisms through metagenomic sequencing combined with environmental factor analysis in this study. The results showed that the distribution of ARGs in urban and rural estuaries differed significantly (<i>p</i>&lt;0.05), the total abundance of ARGs in urban estuaries was significantly higher than that in rural estuaries, and <i>sulfonamides</i> (<i>sul1, sul2</i>) and <i>tetracyclines</i> (tetM) genes were enriched in the urban estuaries, whereas <i>tetracycline-cycloheximidyl C</i> (TcmCs) and <i>vancomycin</i> (VCM) genes were dominant in the rural estuaries. Redundancy analysis (RDA) showed that total dissolved solids (TDS), oxidation reduction potential (ORP) and salinity (S) cumulatively explained 71.59% of the spatial variation in ARGs. The biased Mantel test indicated that socioeconomic factors (<i>e.g.</i>, population density, number of industrial factories) indirectly drove the propagation of ARGs by altering environmental media. This study reveals the environmental driving mechanism of ARGs distribution in urban and rural estuaries of Jiaozhou Bay, and provide a scientific basis for the integrated land-sea management of ARGs in semi-enclosed bays, which is of significance for the ecological risk management of similar estuaries around the world.</p>