This review systematically summarizes the occurrence characteristics of combined antibiotic and pesticide pollution in environmental media during the pond-cleaning period, and reveals three core mechanisms by which combined pollution drives the dissemination of antibiotic resistance genes (ARGs). First, antibiotics and pesticides exert synergistic selective pressure through cross-resistance and co-resistance effects, thereby selectively enriching resistant phenotypes. Second, oxidative stress mediated by combined pollutants activates the bacterial SOS response, increases cell membrane permeability, and enhances the frequency of horizontal gene transfer. Third, niche-filling effects under combined pollution stress drive microbial community succession and promote the enrichment of high-risk ARG host bacteria. Meanwhile, the pulsed drainage pattern during the pond cleaning period facilitates the release of ARGs from sediments, accelerates the dissemination of the resistome into receiving water bodies, and poses unpredictable biosafety risks. Therefore, it is recommended to construct risk assessment models incorporating pulse effects and to adopt an integrated prevention and control strategy involving source substitution, process interruption, and in situ remediation, so as to provide important support for the coordinated management of emerging contaminants and the green and healthy development of aquaculture in China.