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To ensure physician readiness for practice and leadership in changing health systems, an emerging three-pillar framework for undergraduate medical education integrates the biomedical and clinical sciences with health systems science, which includes population health, health care policy, and interprofessional teamwork. However, the partnerships between medical schools and health systems that are commonplace today use health systems as a substrate for learning. Educators need to transform the relationship between medical schools and health systems. One opportunity is the design of authentic workplace roles for medical students to add relevance to medical education and patient care. Based on the experiences at two U.S. medical schools, the authors describe principles and strategies for meaningful medical school–health system partnerships to engage students in value-added clinical systems learning roles. In 2013, the schools began large-scale efforts to develop novel required longitudinal, authentic health systems science curricula in classrooms and workplaces for all first-year students. In designing the new medical school–health system partnerships, the authors combined two models in an intersecting manner—Kotter’s change management and Kern’s curriculum development steps. Mapped to this framework, they recommend strategies for building mutually beneficial medical school–health system partnerships, including developing a shared vision and strategy and identifying learning goals and objectives; empowering broad-based action and overcoming barriers in implementation; and generating short-term wins in implementation. Applying this framework can lead to value-added clinical systems learning roles for students, meaningful medical school–health system partnerships, and a generation of future physicians prepared to lead health systems change.