Antimicrobial resistance (AMR) poses a serious threat to public health, with the emergence of extended-spectrum beta-lactamases (ESBLs) in Enterobacteriaceae, particularly Escherichia coli, raising significant concerns. This study aims to elucidate the drivers of antimicrobial resistance, and the global spread of cefotaxime-resistant E. coli (CREC) strains. Whole-genome sequencing (WGS) was performed to explore genome-level characteristics, and phylogenetic analysis was conducted to compare twenty CREC strains from this study, which were isolated from broiler chicken farms in Bangladesh, with a global collection (n = 456) of CREC strains from multiple countries and hosts. The MIC analysis showed over 70% of strains isolated from broiler chickens exhibiting MIC values ≥ 256 mg/L for cefotaxime. Notably, 85% of the studied farms (17/20) tested positive for CREC by the end of the production cycle, with CREC counts increasing from 0.83 ± 1.75 log10 CFU/g feces on day 1 to 5.24 ± 0.72 log10 CFU/g feces by day 28. WGS revealed the presence of multiple resistance genes, including bla_CTX-M, which was found in 30% of the strains. Phylogenetic comparison showed that the Bangladeshi strains were closely related to strains from diverse geographical regions and host species. This study provides a comprehensive understanding of the molecular epidemiology of CREC. The close phylogenetic relationships between Bangladeshi and global strains demonstrate the widespread presence of cefotaxime-resistant bacteria and emphasize the importance of monitoring AMR in food-producing animals to mitigate the spread of resistant strains.