Marine sediments are recognized as crucial reservoirs of antibiotic resistance genes (ARGs). However, the antibiotic resistome in sediments of the East China Sea, an area heavily impacted by human activities, has not been thoroughly studied. Here, we conducted a systematic investigation into the antibiotic resistome in these sediments using metagenomic analysis. Overall, we detected eighty ARG subtypes and nineteen ARG types. Beta-lactams were the dominant ARG type, and Gammaproteobacteria was the main ARG host in this study. Mobile genetic elements (MGEs) were not major drivers of ARG profiles. Although the ARG host communities significantly differed between the spring and autumn (p < 0.05), the antibiotic resistome remained stable across the two seasons. The assembly of ARGs and their hosts was governed by stochastic processes, and a high ratio of stochastic processes implied its crucial role in the assembly and stabilization of the antibiotic resistome. Co-occurrence network analysis revealed an important role of Deltaproteobacteria in the stabilization of ARG profiles across seasons. Environmental parameters (e.g., temperature and density) played certain roles in the stabilization of the antibiotic resistome between spring and autumn. Moreover, nine human pathogen bacteria (HPB) were detected in this study. We also found that the health risks caused by ARGs were relatively higher in the spring. Our results will provide a strong foundation for the development of targeted management strategies to mitigate the further dissemination and spread of ARGs in marine sediments.