Purpose <p>This study conducts a nationwide investigation of antibiotic resistance gene (ARG) distribution in rice paddy soils across China’s major agricultural regions. We aim to quantify spatial heterogeneity in key ARGs, identify their environmental and microbial drivers, and potential bacterial hosts.</p> Materials and methods <p>Soil samples from 24 rice paddies spanning six geographic regions in China. High-throughput sequencing was used to analyze microbial community composition, qPCR was used to quantify key genes (<i>bla</i>_TEM, <i>sul1</i>, <i>tetA</i>, and <i>tetC</i>), and physicochemical analyses were conducted to evaluate soil environmental properties.</p> Results and discussion <p>The results showed significant regional variations in ARG abundance and distribution, influenced by geographic location, agricultural practices, and environmental factors like salinity and oxygen availability. Proteobacteria and Firmicutes were identified as dominant microbial phyla that were strongly correlated with ARG distribution. The findings also indicated that agricultural activities, such as the use of antibiotics and fertilizers, may exacerbate ARG dissemination by altering soil environmental conditions.</p> Conclusions <p>This study highlights the spatial heterogeneity and driving factors of ARGs in Chinese rice paddy soils, emphasizing the need for region-specific agricultural management practices to mitigate ARG spread. These findings provide critical insights for protecting the environment and public health.</p>