Antimicrobial resistance (AMR) is tracked most closely in clinical settings and high-income countries. However, resistant organisms thrive globally and are transmitted to and from healthy humans, animals and the environment, particularly in many low- and middle-income settings. The overall public health and clinical significance of these transmission opportunities remain to be completely clarified. There is thus considerable global interest in promoting a One Health view of AMR to enable a more realistic understanding of its ecology. In reality, AMR surveillance outside hospitals remains insufficient and it has been very challenging to convincingly document transmission at the interfaces between clinical specimens and other niches. In this Review, we describe AMR and its transmission in low- and middle-income-country settings, emphasizing high-risk transmission points such as urban settings and food-animal handling. In urban and food production settings, top-down and infrastructure-dependent interventions against AMR that require strong regulatory oversight are less likely to curtail transmission when used alone and should be combined with bottom-up AMR-containment approaches. We observe that the power of genomics to expose transmission channels and hotspots is largely unharnessed, and that existing and upcoming technological innovations need to be exploited towards containing AMR in low- and middle-income settings.