Emergence and dissemination of bacteria resistant to multiple antimicrobials is currently one of the major global threats to human and animal public health. Veterinary use of antimicrobials in both developing and developed countries is many-fold greater than their use in human medicine and is an important determinant in selection of these resistant organisms. Our findings on antimicrobial use in salmon aquaculture and their impact on the environment and human health are highly relevant in light of the recently outlined National Plan Against Antimicrobial Resistance in Chile. Ninety-five percent of tetracyclines, phenicols and quinolones imported into Chile between 1998 and 2015 were for veterinary use, mostly in salmon aquaculture. Excessive use of antimicrobials at aquaculture sites was associated with antimicrobial residues in marine sediments 8 km distant, and the presence of resistant marine bacteria harboring easily transmissible resistance genes in mobile genetic elements to these same antimicrobials. Moreover, quinolone and integron resistance genes in human pathogens isolated from patients in coastal regions adjacent to aquaculture sites were sequence-identical to genes isolated from regional marine bacteria, consistent with genetic communication between bacteria in these different environments. Passage of antimicrobials into the marine environment can potentially diminish environmental diversity, contaminate wild fish for human consumption, and facilitate the appearance of harmful algal blooms and resistant zoonotic and human pathogens. Our findings suggest that changes in aquaculture in Chile that prevent fish infections and decrease antimicrobial usage will prove a determining factor in preventing human and animal infections with multiply antimicrobial-resistant bacteria in accord with the modern paradigm of One Health.Emergence and dissemination of bacteria resistant to multiple antimicrobials is currently one of the major global threats to human and animal public health. Veterinary use of antimicrobials in both developing and developed countries is many-fold greater than their use in human medicine and is an important determinant in selection of these resistant organisms. Our findings on antimicrobial use in salmon aquaculture and their impact on the environment and human health are highly relevant in light of the recently outlined National Plan Against Antimicrobial Resistance in Chile. Ninety-five percent of tetracyclines, phenicols and quinolones imported into Chile between 1998 and 2015 were for veterinary use, mostly in salmon aquaculture. Excessive use of antimicrobials at aquaculture sites was associated with antimicrobial residues in marine sediments 8 km distant, and the presence of resistant marine bacteria harboring easily transmissible resistance genes in mobile genetic elements to these same antimicrobials. Moreover, quinolone and integron resistance genes in human pathogens isolated from patients in coastal regions adjacent to aquaculture sites were sequence-identical to genes isolated from regional marine bacteria, consistent with genetic communication between bacteria in these different environments. Passage of antimicrobials into the marine environment can potentially diminish environmental diversity, contaminate wild fish for human consumption, and facilitate the appearance of harmful algal blooms and resistant zoonotic and human pathogens. Our findings suggest that changes in aquaculture in Chile that prevent fish infections and decrease antimicrobial usage will prove a determining factor in preventing human and animal infections with multiply antimicrobial-resistant bacteria in accord with the modern paradigm of One Health.