In order to study the pollution status and regularity of antibiotic resistance genes (ARGs), highthroughput sequencing methods were used to analyze the diversity of ARGs along Danjiangkou Reservoir and Hanjiang River in spring and autumn of 2014. 21 and 19 types of ARGs were detected in spring and autumn samples respectively. Among them, 9 types of ARGs were the main types of ARGs content. Bacitracin was the most important ARGs in water, while β-lactam accounted for the highest proportion in the Taocha sampling sites of Danjiangkou Reservoir. The composition difference of ARGs among sampling sites in Water_Autumn samples was smaller than that in spring. NMDS and ANOSIM analysis showed significant seasonal differences in the composition of ARGs. Trimethoprim, polymyxin and multidrug were ARGs which had significant seasonal differences. Correlation analysis found 13 types of ARGs with significantly strong correlations with each other, and the most relevant ARGs were likely to coexist in the same microorganism. In addition, tetracycline and aminoglycoside may be useful as indicators for predicting the relative abundance of ARGs coexisting in the water source region. This study could provide reference for water quality protection and ARGs pollution prevention and management in drinking water source areas.