According to the United Nations Educational, Scientific, and Cultural Organization (UNESCO), culture provides the transformative dimension for ensuring the development process of the United Nations’ 2030 Agenda for Sustainable Development. As one of the key drivers in the implementation of the United Nations’ Sustainable Development Goals, culture ensures a people-centered and context-relevant approach that cuts across a range of policy areas and, thus, in the context of quality education promotes the development of human resources for cultural and environmental sustainability. It is in this context that we report on a study aimed at developing students’ cultural identity and supporting the younger generation in preserving their cultural heritage, whilst learning chemistry concepts at the same time. The culturally responsive transformative teaching (CRTT) model served as a theoretical framework for the research to engage students in culture-based, high school chemistry learning by utilizing specially designed ethnochemistry texts that highlighted the relationship between cultural values and chemistry concepts. Case studies were conducted within the interpretive research paradigm and involved 149 students from four high schools in four Indonesian provinces, namely Banten, west Java, Bangka Belitung, and south Sumatra. In particular, we were interested in understanding how well students engage in this innovative transformative learning model, designed to educate them about cultural sustainability. We generated data by means of students’ reflective journals, semi-structured interviews with students, and classroom observations. In general, the results from the research strongly suggest that students involved in cultural identity reflection, engaged in cultural-based chemistry learning, explored cultural heritage through a chemistry lens, applied social etiquette and ethics, and developed cultural heritage preservation awareness. These are important aspects of cultural sustainability. The results imply that culturally responsive chemistry education has great potential for educating students and empowering them as conservationists of Indonesian culture. Further research on empowering students on cultural sustainability with other ethnochemistry topics within Indonesian cultural contexts is needed to further investigate the CRTT model’s broader efficacy.