Objective This study examined the associations between public health engagement (PHE) in school-based substance use prevention programs and student substance use. For the purposes of this study, PHE refers to any form of collaboration between the local government public health agency and the school to promote the physical and mental health of students. Methods Data for this study were collected from the Cannabis, Obesity, Mental health, Physical activity, Alcohol use, Smoking and Sedentary behaviour (COMPASS) study during the 2018/2019 data collection year. Multilevel logistic regression was used to analyze the associations between PHE and student substance use. Results Data from 84 schools and 42,149 students were included; 70% of schools had PHE in substance use prevention programs. PHE in substance use prevention appears to have had no significant impact on student substance use in our models. When PHE was divided into five methods of engagement, it was found that when public health solved problems jointly with schools, the odds of a student using alcohol or cannabis significantly increased. When schools were split into low- and high-use schools for each substance measured, some methods of PHE significantly decreased the odds of cannabis and cigarette use in high-use schools and significantly increased the odds of alcohol and cannabis use in low-use schools. Conclusion This study highlights the need to develop better partnerships and collaborations between public health and schools, and the importance of ensuring that school-based substance use prevention programs are evidence-based and tailored to the specific needs of schools and students.