Antimicrobial stewardship programmes (ASPs) aim to optimize antibiotic use and prevent antimicrobial resistance. This study assessed the impact of ASPs, initiated using a hub-and-spoke approach, on antibiotic use in Zambian public hospitals. A pre-post study was conducted in 10 ASP-naive hospitals across Zambia using the Centers for Disease Control and Prevention (CDC)'s hospital-based ASP core elements (i.e. leadership, accountability, pharmacy expertise, stewardship actions, tracking progress, reporting and education) checklist and the global point prevalence survey methodology. The intervention involved technical staff from a national 'hub' hospital with an established ASP providing on-site orientation and mentorship to multidisciplinary teams of healthcare workers at 10 'spoke' hospitals to build capacity in antimicrobial stewardship. ASP core elements and inpatient antibiotic use prevalence (AUP) were assessed before and 12 months after ASP implementation. Data were statistically analysed. The adoption of ASP core elements improved significantly (P = 0.001, 95% CI: -17.8 to -5.42). AUP decreased from 50.1% (±5.8, n = 1477) to 44.3% (±4.6, n = 1400) after 12 months, though the reduction was not statistically significant (P = 0.442; 95% CI: -9.8 to 21.6), with 'Watch' list antibiotics remaining the most commonly prescribed across the hospitals. The hub-and-spoke approach successfully catalysed ASPs in public hospitals in Zambia, demonstrating the potential for improving antibiotic use practices over time, provided structural challenges are addressed. This approach and insights can guide stakeholders in Zambia and similar settings in enhancing hospital ASPs.