Different surveillance studies (2005-2015) on the presence of ESBL-producing E. coli in the northwest Spain revealed that eae-positive isolates of serotype O153:H10 were periodically detected in meat (of beef, chicken and pork), and also implicated in human diarrhea. This study aimed: i) to characterize the degree of relatedness between human and animal isolates; ii) to know if this was a geographically restricted or disseminated genetic lineage. Thirty-two isolates were conventionally typified as O153:H10-A-ST10 fimH54, fimAvMT78, traT and eae-beta1, being 21 of those CTX-M-32 or SHV-12 producers. PFGE comparison of their macrorestriction profiles showed high similarity (>85%). The plasmidome analysis revealed a stable combination of IncF (F2:A-:B-), IncI1 (STunknown) and IncX1 plasmid types, together with non-conjugative Col-like. Besides, the core genome investigation based on the cgMLST scheme from Enterobase, proved close relatedness between isolates of human and animal origin. Our results demonstrate that a hybrid MDR aEPEC/ExPEC of clonal group O153:H10-A-ST10 (CH11-54) would be playing a successful role in spreading ESBLs (CTX-M-32) in our region within different hosts, including wildlife. It would be potentially implicated in human diarrhea via food (meat) transmission. Importantly, we proved genomic evidence of a related hybrid aEPEC/ExPEC in other countries.