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Background: The global spread of extended-spectrum β-lactamase (ESβL)-producing Escherichia coli has been considered a One Health issue that demands continuous genomic epidemiology surveillance in humans and non-human hosts., Objectives: To report the occurrence and genomic data of ESβL-producing E. coli strains isolated from South American llamas inhabiting a protected area with public access in the Andean Highlands of Peru., Methods: Two ESβL-producing E. coli strains (E. coli L1LB and L2BHI) were identified by MALDI-TOF. Genomic DNAs were extracted and sequenced using the Illumina NextSeq platform. De novo assembly was performed by CLC Genomic Workbench and in silico prediction was accomplished by curated bioinformatics tools. SNP-based phylogenomic analysis was performed using publicly available genomes of global E. coli ST10., Results: Escherichia coli L1LB generated a total of 4 000 11 and L2BHI a total of 4 002 54 paired-end reads of ca.164 × and ca. 157 ×, respectively. Both E. coli strains were assigned to serotype O8:H4, fimH41, and ST10. The bla CTX-M-65 ESβL gene, along with other medically important antimicrobial resistance genes, was predicted. Broad virulomes, including the presence of the astA gene, were confirmed. The phylogenomic analysis revealed that E. coli L1LB and L2BHI strains are closely related to isolates from companion animals and human hosts, as well as environmental strains, previously reported in North America, South America, Africa, and Asia., Conclusion: Presence of ESβL-producing E. coli ST10 in South American camelids with historical and cultural importance supports successful expansion of international clones of priority pathogens in natural areas with public access., (Copyright © 2023. Published by Elsevier Ltd.)