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<div> Introduction Learning beyond the classroom is important for holistic engagement in antimicrobial resistance(AMR) mitigation. Extracurricular interventions can catalyze multidisciplinary engagement and inspire innovative solutions. This study aimed to determine the knowledge, attitudes, and motivations influencing medical students’ engagement in AMR Club initiatives at Busitema University, Uganda. Methodology This was a descriptive cross-sectional study conducted at Busitema University among undergraduate students pursuing Bachelors of Medicine and Surgery, Bachelor of Science in Nursing, and Bachelor of Science in Anesthesia and Critical care. Data collection was performed using a semi-structured, pre-tested questionnaire and administered to the participants The Bloom’s cut-off method was used to analyse the knowledge of the participants, while bivariate analysis was conducted using the chi square test. Multivariable logistic regression analysis was used to identify factors independently associated with students’ engagement in AMR club activities. Results Of the 193 study participants, 71.5%(n) demonstrated sufficient knowledge about antimicrobial resistance (AMR), as determined using Bloom’s cutoff categories (≥60% classified as sufficient, <60% as insufficient), with an average knowledge score of 68.18% (SD ±16.12). Additionally, 90% of participants acknowledged the significance of incorporating AMR topics into their curriculum, while 87.5% emphasized the need for AMR training using a One Health approach. The major motivations for students to engage in extracurricular activities addressing AMR were peer influence (n = 42), university support (n = 35), and inspiration drawn from peer mentors’ work (n = 35). Conclusion The students demonstrated a high level of knowledge and positive attitudes towards AMR but highlighted the need for further in-depth training. Participation in extra-curricular activities such as involvement in an AMR Club, was found to significantly influence students’ engagement in AMR related interventions. </div>