In both the United States and Europe, concerns have been raised about whether preservice and in-service training succeeds in equipping teachers with the professional knowledge they need to deliver consistently high-quality instruction. This article investigates the significance of teachers’ content knowledge and pedagogical content knowledge for high-quality instruction and student progress in secondary-level mathematics. It reports findings from a 1-year study conducted in Germany with a representative sample of Grade 10 classes and their mathematics teachers. Teachers’ pedagogical content knowledge was theoretically and empirically distinguishable from their content knowledge. Multilevel structural equation models revealed a substantial positive effect of pedagogical content knowledge on students’ learning gains that was mediated by the provision of cognitive activation and individual learning support.