Equipping future change agents with the competencies to lead the societal transformation towards sustainability requires competent and committed teachers who effectively implement Education for Sustainable Development (ESD) across the education system. In a comparative case study, this paper investigates how individual ESD courses in teacher education programs at Leuphana University (Germany) and Arizona State University (USA) support the development of ESD-specific professional action competence for teachers. Applying a mixed-method approach, the specific focus is on the links between supporting or hindering factors that affect pre-service teachers’ actual achievement of intended learning outcomes. The findings indicate that both courses increased students’ competence—yet, to varying degrees. The 4Cs (personal, professional, social, and structural connections) were revealed as the most significant factors affecting students’ learning and should be considered when designing course offerings in Teacher Education for Sustainable Development (TESD) with the goal to develop students’ knowledge, skills, and attitudes.