Antibiotic resistance genes (ARGs) have been identified as emerging pollutants in the environment. However, little information is available for ARGs in natural wetlands at high altitude. In this study, we investigated 32 wetlands across the Qinghai-Tibetan Plateau, with the variation of wetland types, altitude, and environmental factors, to assess the determinant factor of ARGs in this area. ARGs were detected in all the wetlands, ranged from 1.80 x 105 to 1.35 x 107 copies per gram of soils. The ARGs in wetland soils were diverse and abundant, and varied from each site, but the spatial geographical distance did not influence the ARG profile. The mobile genetic elements in wetlands ranged from 3.13. x 103 to 1.02 x 106 copies per gram of soil, indicating the low abundance of mobile genetic elements suggests a lower transfer rate of ARGs between bacteria in the Plateau. Bacterial community composition was the main driver in shaping the ARG diversity and geographic distribution. Soil moisture and temperature were positively correlated with ARG abundance in this region. These results not only provide a better understanding of the background levels of ARGs in the Qinghai-Tibetan Plateau, but also shed light on the influence of climate change and increased human activities on the distribution of ARGs.