: Antimicrobial resistance (AMR) poses a critical global health challenge, particularly in resource-limited settings. A hub-and-spoke model, decentralising expertise and distributing resources to peripheral facilities, has been proposed as a strategy to enhance the antimicrobial stewardship (AMS) capacity in low- and middle-income countries. : This study sought to understand healthcare professionals' experiences of a hub-and-spoke AMS model in the Volta Region of Ghana and its influence on clinical practice, leadership, and collaborative endeavours to address AMR. : A qualitative descriptive design was adopted. In-depth interviews were conducted with 11 healthcare professionals who participated in the AMS program. Thematic analysis was used to identify key themes related to the knowledge and skills that were gained, clinical and leadership practice changes, capacity building, and challenges. : Participants reported an increased awareness of AMR, particularly regarding the scale and clinical implications of antimicrobial misuse. The clinical practice improvements included more judicious prescribing and enhanced adherence to infection prevention and control measures. Many respondents highlighted stronger leadership skills and a commitment to capacity building through AMS committees, multidisciplinary collaboration, and cross-organisational knowledge exchange. Despite resource constraints and logistical hurdles, participants expressed optimism, citing data-driven approaches such as point prevalence surveys to track progress and inform policy. Engagement with hospital management and public outreach were viewed as essential to sustaining AMS efforts and curbing over-the-counter antibiotic misuse. : The hub-and-spoke model caused observable improvements in AMS knowledge, clinical practice, and leadership capacity among healthcare professionals in Ghana. While challenges remain, particularly in securing sustainable resources and shifting community behaviours, these findings underscore the potential of network-based programs to catalyse systemic changes in tackling AMR. Future research should explore long-term outcomes and strategies for embedding AMS practices more deeply within healthcare systems and communities.