Introduction Community distribution of medications in low- and middle-income countries has been shown to accelerate the emergence of antimicrobial resistance. The distribution of medications is often carried out by private vendors operating under constrained conditions. Yet patterns in medicine distribution—and their consequences—are not well understood. The aim of this study was to illuminate the challenges reported by employees of chemical shops and pharmacies throughout Accra. Our objectives are twofold: to 1) assess obstacles and challenges faced by medicine vendors during their sales of antibiotic and antimalarial medications, and 2) identify opportunities for improving community-level stewardship of antimicrobials. Methods Responses to open-ended questions from a survey of 80 shopkeepers in pharmacies and chemical shops throughout Accra were analyzed using the socioecological model of public health. Results Overall, shopkeepers most often reported constraints at the interpersonal and community levels of the socioecological model of public health. These included the prohibitive costs of medicines, customer attitudes, and customers’ attempts at self-medication and uninformed antimicrobial use. Other challenges included a lack of diagnostic testing, supply chain issues, and the larger economic and healthcare situation of the community. Discussion The safe and effective distribution of medications was truncated by three main sources of obstacles: financial insecurity among customers, challenges directly in the treatment of illnesses, and broader issues with the fragmented healthcare infrastructure affecting shopkeepers’ roles as health educators and gatekeepers of medicines. Conclusion These context-specific findings identify tractable challenges faced by medicine vendors in Ghana, with relevance to antimicrobial stewardship across resource-poor settings globally. Addressing barriers faced by shopkeepers would provide an opportunity for significantly improving the provision of medications, and ultimately healthcare, at the community level. Such efforts will likely expand access to populations who may otherwise be unable to access services in formal institutions of care.