Hand hygiene serves as a critical preventative measure against the spread of acquired infections in healthcare facilities and is an integral component of patient safety programs. While healthcare students in training are typically introduced to the principles underlying hand hygiene, the translation of this understanding into practice is often lacking, and compliance has remained low. This study aimed to evaluate health science students' in biomedical sciences, chiropractic and emergency medical care, environmental health, complementary medicine, medical imaging and radiation sciences, nursing, optometry, podiatry, and sports and movement studies perceptions regarding hand hygiene education (knowledge and attitude) and practice at a university in South Africa. Consenting students were asked to complete an online questionnaire that tested their knowledge, practices, and skills in handwashing. The ANOVA analysis results suggested significant differences in hand hygiene scores across departments and years of study. The multiple regression analyses confirmed these findings, suggesting that the department of study significantly influenced all aspects of hand hygiene, while the year of study affected hand hygiene skills, and age group influenced hand hygiene practices. Based on these findings, a conceptual model, the University Hand Hygiene Improvement Model (UHHIM), was proposed to enhance the teaching and learning of hand hygiene at the university level. The model underscores the necessity of targeted education, continuous monitoring, and feedback, and the pivotal roles of hand hygiene facilitators and student participation in enhancing hand hygiene behaviors.