BACKGROUND: Antimicrobial resistance (AMR) poses a significant threat to the world and could become humanity's next major challenge. This study assessed non-healthcare students' knowledge, attitude and practices (KAP) towards antimicrobial use (AMU) and AMR at the University of Zambia. METHODS: This cross-sectional study was conducted among 443 non-healthcare students from August to October 2022 using a structured questionnaire. Data analysis was done using IBM SPSS version 24.0. RESULTS: Of the 433 participants, 55.2%, 63.5% and 45% had moderate KAP scores regarding AMU and AMR. The prevalence of self-medication with antibiotics was 76.7%. Male participants were less likely to have good knowledge (OR = 0.524, 95% CI: 0.347-0.792) and positive attitudes (OR = 0.585, 95% CI: 0.364-0.940) towards AMU and AMR compared with females. Students who were studying Engineering and Mining were more likely to have good knowledge of AMR (OR = 1.891, 95% CI: 1.197-2.987) compared with those in Social Sciences. Those who were in their fourth and fifth years were more likely to have positive attitudes towards AMU and AMR (OR = 1.851, 95% CI: 1.147-2.986) compared with those who were in the first, second and third years. Finally, students who practised self-medication were less likely to have good self-reported practice towards AMR (OR = 0.442, 95% CI: 0.278-0.702) compared with those who did not. CONCLUSIONS: This study demonstrated that non-healthcare students had moderate KAP regarding AMU and AMR. All university students should be provided with education about AMU and AMR through free short courses, seminars, workshops, and AMR and antimicrobial stewardship awareness campaigns.