Smallholder farms are the predominant livestock system in India. Animals are often kept in close contact with household members, and access to veterinary services is limited. However, limited research exists on how antibiotics are used in smallholder livestock in India. We investigated antibiotic supply, usage, and their drivers in smallholder livestock production systems, including crossover-use of human and veterinary antibiotics in two rural sites in West Bengal. Qualitative interviews were conducted with key informants (n = 9), livestock keepers (n = 37), and formal and informal antibiotic providers from veterinary and human health sectors (n = 26). Data were analysed thematically and interpreted following a One Health approach. Livestock keepers and providers used antibiotics predominantly for treating individual animals, and for disease prevention in poultry but not for growth promotion. All providers used (highest priority) critically important antimicrobials for human health and engaged in crossover-use of human antibiotic formulations in livestock. Inadequate access to veterinary drugs and services, and a perceived efficacy and ease of dosing of human antibiotics in animals drove crossover-use. Veterinary antibiotics were not used for human health due to their perceived adverse effects. Given the extent of usage of protected antibiotics and crossover-use, interventions at the community level should adopt a One Health approach that considers all antibiotic providers and livestock keepers and prioritizes the development of evidence-based guidelines to promote responsible use of antibiotics in animals.