Antibiotic resistance genes (ARGs), emerging environmental contaminants, have become challenges of public health security. However, the distribution and drivers of ARGs, especially high-risk ARGs, in large-scale aquaculture sediments remain unknown. Here, we collected sediment samples from 40 crayfish ponds in seven main crayfish culture provinces in China and then investigated the distribution and risk of ARGs based on high-throughput sequencing and quantitative PCR techniques. Our results suggested that aquaculture sediment was potential reservoir of ARGs and the abundance of aadA-02 was the highest. High-risk ARG (floR) was also prevalent in the sediment and was the most abundant in Jiangsu Province, where opportunistic pathogens were also enriched. The abundance of floR was positively correlated with different environmental factors, such as total phosphorus in water and total carbon in sediment. In addition, Mycobacterium sp., opportunistic pathogenic bacteria, might be potential host for floR. Furthermore, the potential propagation pathway of ARGs was from sediment to crayfish gut, and Bacteroidetes and Proteobacteria might be the main bacterial groups responsible for the proliferation of ARGs. Generally, our results illustrate that pond sediment may be an ARG reservoir of aquatic animals. Meanwhile, our study helps develop valuable strategies for accessing risks and managing ARGs.