As concerns about the prevalence of infections that are resistant to available antibiotics increase, attention has turned toward the use of these medicines both within and outside of formal healthcare settings. This article analyses findings from mixed-methods anthropological studies of antibiotic use in households in a range of rural and urban settings in Zimbabwe, Malawi and Uganda between 2018 and 2020. The most self-reported ‘frequently used’ antibiotics across settings were amoxicillin, cotrimoxazole and metronidazole. The stories behind their use varied between settings, reflecting differences in the configuration of health systems and antibiotic supplies. At the same time, these stories reveal cross-cutting features and omissions of contemporary global health programming that shape the contours of antibiotic (over)use at national and local levels.