Science educators have presented numerous conceptual and theoretical arguments in favor of teaching science through the exploration of socio-scientific issues (SSI). However, the empirical knowledge base regarding the extent to which SSI-based instruction supports student learning of science content is limited both in terms of the number of studies that have been conducted in this area and the quality of research. This research sought to answer two questions: (1) To what extent does SSI-based instruction support student learning of science content? and (2) How do assessments at variable distances from the curriculum reveal patterns of learning associated with SSI-based instruction? Sixty-nine secondary students taught by three teachers participated in the study. Three teachers implemented an SSI intervention focused on the use of biotechnology for identifying and treating sexually transmitted diseases. We found that students demonstrated statistically and practically significant gains in content knowledge as measured by both proximal and distal assessments. These findings support the claim that SSI-based teaching can foster content learning and improved performance on high-stakes tests.