Abstract: The extensive use of antibiotics and their accumulation in aquatic environments not only directly threaten river and lake ecosystems and human health, but also elevate environmental risks by accelerating the spread of antibiotic resistance genes (ARGs). To systematically understand the pollution status, dissemination mechanisms, and potential risks of antibiotics and ARGs, relevant literature from the China National Knowledge Infrastructure (CNKI) and Web of Science (WoS) databases covering the period from 2000 to 2023 was collected, bibliometric tools were employed to analyze the research trends and hotspots over the past more than two decades, and the sources, contamination characteristics, and ecological risks of antibiotics and ARGs in river and lake environments, as well as their interactions with other pollutants, were reviewed. The results showed that: (1) Antibiotics commonly detected in aquatic environment include sulfonamides (SAs), tetracyclines (TCs), quinolones (QNs), and macrolides (MLs), which are primarily sourced from medical effluents, agricultural runoff, domestic wastewater, and livestock manure. ARGs primarily spread among bacterial strains through antibiotic induction and horizontal gene transfer (HGT). The distribution of antibiotics and ARGs is influenced by various factors, including regional natural characteristics, socioeconomic status, and environmental conditions. (2) The solid-liquid partitioning, degradation, and migration of antibiotics are comprehensively regulated by their intrinsic properties, the physicochemical properties of the aqueous environment, and external driving forces. The enrichment and dissemination of ARGs in aquatic environments are closely related to microbial metabolism, external selection pressures, and HGT mediated by mobile genetic elements (MGEs). (3) Current environmental risk assessments of antibiotics are primarily conducted using the risk quotient (RQ) method and the species sensitivity distribution (SSD) method. However, regarding the exacerbated risks caused by the interactions between antibiotics, ARGs, and co-occurring pollutants (such as heavy metals and microplastics), a more comprehensive assessment framework, supplemented by bioinformatics tools, is needed to identify the potential threats associated with these interactions. Future research should adopt a systems perspective to enhance the comprehensive understanding of the environmental behavior of antibiotics and ARGs under complex environmental conditions, thereby promoting the synergistic optimization of risk assessment methods and regulatory strategies. It will provide support for the scientific management of antibiotic-related risks in complex aquatic environments.