We report the occurrence and genomic analysis of extended-spectrum β-lactamase (CTX-M)-producing Escherichia coli in anthropogenically polluted coastal waters of Southeast Brazil. E. coli strains belonging to sequence types (STs) ST10, ST38, ST155 and ST1284 exhibited a wide resistome, with genes conferring resistance to medically relevant antimicrobials and heavy metals, and a halophilic behavior (tolerance to 9–10% NaCl). These findings suggest a heavy contamination in this area by critical priority bacteria adapted to marine environments, which might have negative impacts on human and ocean health. •Occurrence of MDR bacteria in urban-impacted coastal waters has been investigated.•Presence of halotolerant CTX-M-producing E. coli is highlighted.•Genomic analysis revealed several genes conferring resistance to antimicrobials and heavy metals.•Dissemination of CTX-M-producing bacteria in marine ecosystems has been discussed.