This paper presents the findings of the qualitative component of a combined methods research study that explores a range of individual and school factors that influence the uptake of chemistry and physics in post-compulsory study in England. The first phase involves using the National Pupil Database to provide a sampling frame to identify four matched pairs of high-uptake and low-uptake schools by salient school factors. Case studies of these eight schools indicate that students employ selection strategies related to their career aspirations, their sense of identity and tactics, and their prior experience. The school factors influencing subject choice relate to school management, student support and guidance, and student empowerment. The most notable differences between students in high-uptake and low-uptake schools are that students in high-uptake schools appear to make a proactive choice in relation to career aspirations, rather than a reactive choice on the basis of past experience. Schools with a high uptake offer a diverse science curriculum in the final two years of compulsory study, set higher examination entry requirements for further study and, crucially, provide a range of opportunities for students to interact with the world of work and to gain knowledge and experience of science-related careers.