Abstract: Objective To evaluate the antibiotics resistance characteristics and molecular epidemiological features of Escherichia coli in whole chickens retailed in Beijing, including resistance rates, resistance profile, serotypes, sequence types (STs), major resistant genes and plasmids distribution. Methods: E. coli was isolated from whole chickens, and was subjected to antimicrobial susceptibility tests. Cefotaxime (CTX)-resistant strains were selected for whole-genome sequencing, and bioinformatics methods were used to analyze the genomic characteristics of the strains. Results: A total of 202 E. coli strains were isolated from 87 samples, with a sample positive rate of 87.4%. 83.2% of the strains showed varying degrees of resistance to detected antibiotics, with the highest resistance rate to tetracycline (76.2%), and 65.3% of the strains were multi-drug resistant. Genomic analysis of 38 CTX-resistant strains from different samples identified 28 serotypes and 29 STs, with core genome multi-locus sequence typing revealing high genetic diversity. The primary resistance genes were: the ESBL-encoding gene blaCTX-M-65 (44.7%, 17/38) for β-lactam antibiotics, and the plasmid-mediated qnrS1 (47.4%, 18/38) and chromosomal mutation GyrA_S83L (76.3%, 29/38) for quinolones. Additionally, 78.9% of the strains exhibited concurrent resistance to third-generation cephalosporins and quinolones. Plasmid analysis indicated that the IncFIB type was the most prevalent (81.6%, 31/38). Conclusion: The positive rate of E. coli in retailed whole chickens in Beijing is high, with strains displaying multidrug resistance. These strains carry multiple resistance genes, posing a risk of plasmid-mediated horizontal gene transfer. These findings highlight the need to strengthen food safety regulations and promote the rational use of antibiotics.