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The presence and distribution of antibiotics and antibiotic resistance genes (ARGs) in rivers have attracted significant global concern. However, research on the contamination of typical rivers in Sichuan Province, China, remains limited. This study aimed to assess the residual levels of antibiotics across 42 national and provincial monitoring sites in nine rivers within Sichuan using UPLC-MS/MS. Ecological risk levels were evaluated through established risk assessment methods, and antibiotic resistance in Escherichia coli(E.coli) isolated from these waters was determined using the Kirby-Bauer disk diffusion method. Additionally, redundancy analysis (RDA) was conducted to explore the impact of residual antibiotics on the microbial community structure in the Minjiang River basin. Antibiotics were detected in all nine rivers studied, with the Minjiang, Tuojiang, and Jialingjiang rivers exhibiting particularly severe contamination, with concentrations ranging from 0.29 to 2233.71 ng/L. The level of antibiotic pollution in the Sichuan Basin was significantly higher than in other regions of Sichuan, likely due to the area's high population density. Furthermore, 9.77% of E. coli isolates from the nine rivers exhibited antibiotic resistance, with over 5.8% demonstrating multidrugs resistance. Norfloxacin, amoxicillin, ampicillin, and tetracycline were identified as the primary contributors to the high ecological risk at 26 of the 42 monitoring sites. A strong correlation was observed between residual antibiotics and changes in microbial community structure. These findings provide critical insights into the distribution of antibiotics and ARGs in the rivers of Sichuan Province and highlight the urgent need for targeted strategies to mitigate antibiotic pollution. Addressing this issue is essential to protect both ecological integrity and public health. [ABSTRACT FROM AUTHOR]