Microplastics (MPs) ubiquitous in environments promote the dissemination of antibiotic resistance genes (ARGs), threatening ecosystem safety and human health. However, quantitative assessments of the health risks of ARGs (HRA) in plastisphere and an in-depth exploration of their driving mechanisms are still lacking. Here, the microbiomes, ARGs, and community assembly processes of five types of MPs in an urbanizing watershed were systematically investigated. By fully considering the abundance, clinical availability, human pathogenicity, human accessibility, and mobility of 660 ARGs in plastisphere, the HRA on MPs were quantified and compared. Polyethylene had the highest HRA among the five MP types, and urbanization further increased its risk index. In addition to abiotic factors, more complex biotic factors have been shown to drive HRA in plastisphere. Specifically, dispersal limitation accounted for the increasing diversity and interaction of bacteria that determined HRA in plastisphere. Further analysis of metabolic functions indicated that a higher HRA was accompanied by decreased normal metabolic functions of plastisphere microbiota due to the higher fitness costs of ARGs. This study advances the quantitative surveillance of HRA in plastisphere and understanding of its driving mechanisms. This will be helpful for the management of both MPs and ARGs treatments for human health.