This case study explores how a group of Grade 9 students engaged in sociopolitical discourses and actions in a science class in a mostly indigenous student school in Nepal. The study used sociopolitical consciousness (SPC) as a framework to document and understand indigenous students' SPC-oriented science interactions and subsequent social change actions. We used ethnographic methods of data collection over 6 months. The study focused on the actions of 4 girls and 2 boys belonging to the indigenous Tharu group. Data were analyzed using iterative qualitative methods. The study findings show that students are capable of engaging in critical thinking, critical reflecting, and taking actions for social change. Additionally, students are competent to link their experiences with social, structural, and political discrimination to the relevant science content they learn. The study presents four thematic findings related to SPC and science teaching and learning: Fostering social justice awareness in science class, fostering structural understanding of inequities in sickle cell disease, fostering sociopolitical actions for sickle cell disease, and the teacher's activist pedagogy for SPC in science learning. Implications of the study are that culturally relevant pedagogy helps indigenous students to become sociopolitically more aware of the links between science and social change. Adding aspects of critical pedagogies in science teaching could encourage students to become more sociopolitically reflective about science learning.