Escherichia coli ST410 (Ec-ST410) is an emerging, multidrug-resistant clone. Recent investigations of its global epidemiology and evolution have been based almost exclusively on isolates from Europe and North America. It is unclear whether Southeast Asian-origin Ec-ST410 (SEA-Ec-ST410) belong to these same clones or represent regionally disseminated variants. Antimicrobial resistance mechanisms among SEA-Ec-ST410 were characterised, and whether they belonged to regional variants was investigated by contextualising them within a global collection. Seven Ec-ST410 were identified among a recent collection of expanded-spectrum cephalosporin-resistant E. coli recovered from 91 healthy women (stool) and 26 infected patients (blood and urine) living in Phnom Penh, Cambodia. Nine additional Ec-ST410 genomes were identified from Thailand (n = 7) and Vietnam (n = 2) through EnteroBase and PubMed searches. The assembled genomes were characterised and a SNP-based phylogenetic tree was created comparing these 16 SEA-Ec-ST410 with a previously published Ec-ST410 collection, primarily sourced from Europe (97/128) and North America (24/128). SEA-Ec-ST410 belonged to several distinct branches within previously described clonal clades. SEA-Ec-ST410 within the B3/H24Rx sublineage encoded blaCTX-M-55 (8/12) and F18:A-:B1 plasmid replicons (6/12), neither of which were detected among other Ec-ST410 belonging to this clade. Three of four SEA-Ec-ST410 within the B4/H24RxC sublineage lacked both blaOXA-181 and an IncX3 plasmid replicon that were harboured by 97% and 100% of all other Ec-ST410 in this sublineage (n = 64), respectively. In conclusion, Ec-ST410 are present in Southeast Asia following multiple introductions. The unique pattern of antimicrobial resistance elements harboured by SEA-Ec-ST410 suggests independent circulation in the region.