Chemical safety, a practice of protecting humans and the environment in which they work and live from the deleterious effects of chemical substances, was investigated in this study in Nigerian secondary schools. Using a mixed-method survey, we investigated the awareness level and implementation of the best practices of chemical safety by 1246 senior secondary school chemistry students. Students in rural schools were found to have a lower level of awareness of chemical safety compared to the students in urban schools. Statistically significant differences were found in all except one of the awareness measures--washing hands before practicals and after leaving the chemistry lab. Urban students were more in breach of chemical safety practices than students in rural schools. Most of the observed differences were statistically significant (p < 0.001). Interview (qualitative) data from 20 students show four emerging themes to explain the findings, including a low level of chemistry laboratory resourcing, poor chemical safety training of the teachers, inadequacies in safety tools, charts, and kits, and weak enforcement of safety regulations. Based on the data from the study, recommendations were made for bolstering the awareness level of students in chemical safety and their chemical safety practices. These include the incorporation of chemical safety in the core curriculum, requiring quality assurance entities to enforce resourcing of basic safety equipment to schools, government-directed workshops on the need for chemical safety, and requiring teachers to provide chemical hazards information to students.