This systematic review investigates the relevance of general pedagogical knowledge for successful teaching. It synthesises the empirical evidence of 10 769 teaching professionals and 853 452 students from primary to tertiary education in 21 countries. The meta-analysis of 20 quantitative studies revealed significant effects for teaching quality and student outcomes (Cohen’s d = .64 and .26), indicating that more knowledgeable teachers achieve a three-month additional progress for students. The three themes emerging from 31 qualitative studies underline that general pedagogical knowledge is a crucial resource for teaching. Results also show that teaching requires knowledge about a range of topics, specific skills and other competences to transform knowledge into practice. Teachers need training and practical experience to acquire knowledge, which they apply according to the pedagogical situation at hand. The results allow for important conclusions for policy, practice and research.