A high-risk clone is defined as being globally distributed, associated with multiple antimicrobial resistance determinants, able to colonise and persist in the host, capable of effective transmission between hosts, has enhanced pathogenicity and fitness, and can cause severe and/or recurrent infections. Since 2024, third-generation cephalosporin-resistant (3GC-R) E. coli has been included in the critical group of the WHO Bacterial Priority Pathogens List. This study aimed to determine the presence of high-risk clones among the highest priority critically important antimicrobials (HPCIA)-resistant E. coli isolated from fresh pork meat from butcher shops in La Plata, Buenos Aires, Argentina. Whole genome sequencing was performed on 85 HPCIA-resistant E. coli isolates, obtained from 46 butcher shops in La Plata. Of these, 27 belonged to nine clones described as High Risk: ST101 (n=5), ST10 (n=4), ST48 (n=4), ST744 (n=4), ST23 (n=3), ST58 (n=2), ST88 (n=2), ST117 (n=2) and ST410 (n=1) and 12 of them were 3GC-R. Resistance was mediated by bla_CTX-M-55 (n=7), bla_CTX-M-14 (n=4) and bla_CMY-2 (n=1). E. coli harbouring bla_CTX-M-55 belonged to ST10, ST23, ST58, ST88 and ST117. These were also fosfomycin-resistant mediated by fosA3 (n=3) and fosL1 (n=2), and potentially ciprofloxacin-resistant by plasmid-mediated quinolone resistance genes qnrB19 and qnrS1 (n=4). E. coli harbouring bla_CTX-M-14 (n=4) belonged to ST23 and ST101 and were potentially ciprofloxacin-resistant due to qnrS1 carriage. E. coli harbouring bla_CMY-2 belonged to ST48, and all were fluoroquinolone-resistant, with one carrying qnrS1 (n=1). The detection of high-risk clones in food products underscores the risk of transmission and highlights the urgent need for control strategies to mitigate the spread of pathogens implicated in cross-contamination and food safety, highlighting the importance of implementing good manufacturing practices.