Medical education can have significant negative effects on the well-being of medical students. To date, efforts to improve student mental health have focused largely on improving access to mental health providers, reducing the stigma and other barriers to mental health treatment, and implementing ancillary wellness programs. Still, new and innovative models that build on these efforts by directly addressing the root causes of stress that lie within the curriculum itself are needed to properly promote student wellness. In this article, the authors present a new paradigm for improving medical student mental health, by describing an integrated, multifaceted, preclinical curricular change program implemented through the Office of Curricular Affairs at the Saint Louis University School of Medicine starting in the 2009–2010 academic year. The authors found that significant but efficient changes to course content, contact hours, scheduling, grading, electives, learning communities, and required resilience/mindfulness experiences were associated with significantly lower levels of depression symptoms, anxiety symptoms, and stress, and significantly higher levels of community cohesion, in medical students who participated in the expanded wellness program compared with those who preceded its implementation. The authors discuss the utility and relevance of such curricular changes as an overlooked component of change models for improving medical student mental health.