Background: Many students enter into postsecondary education without the college readiness skills that allow them to face the demands of postsecondary education. Increasingly, policymakers and educational researchers are responding to calls for reforming secondary education to provide more opportunity for all students to receive high quality education and to become career and college ready. Purpose: This study attempts to identify levers to increase student performance in secondary education. In particular, it examines relationships of school, teaching, teacher, and teacher professional development characteristics with student scores on high-stakes Advanced Placement (AP) examinations in the sciences.Setting: This study is situated in the context of the large-scale, top-down, nationwide AP curriculum and examination reform in the sciences (Biology, Chemistry, Physics) in the United States. This is an unprecedented opportunity to analyze changing educational landscapes in the United States with large-scale national student-, teacher-, school-, and district-level data sets across multiple science disciplines and different stages of the curriculum reform implementation connected to a standardized and high-stakes student outcome measure.Population: This study analyzes nationwide data samples of the AP Biology, AP Chemistry, and AP Physics population during the first, second, and third year of the curriculum reform implementation. Across disciplines and years, the analytical samples include a total of 113,603 students and 6,046 teachers. Research design: This empirical quantitative study uses data from web-based surveys sent to all AP science teachers. Additionally, College Board provided student- and school-level data for all students taking AP examinations. Data preparation methods included exploratory and confirmatory factor analysis. Associations towards student achievement were analyzed through multi-level ordered logistic regression analysis separately by science discipline and year of the curriculum reform implementation. Afterwards, the results were aggregated through a meta-analysis. Findings: Student performance is not pre-determined by students’ background, leaving roughly 60% of the AP score variance potentially malleable for teacher and school-level factors. In particular, teachers’ perceived administrative support, self-efficacy, teaching experience, and elements of classroom instruction were related to student performance. Notably, teachers’ professional development participation has a small, mixed impact on student achievement. Conclusion: The identified levers for improving student achievement provide a strong rationale for the continued efforts of policy makers to improve school environments and to support science teachers to ultimately both increase student learning and help all students graduate prepared for college and ready for their future careers.