Objective: On the occasion of the American College Health Association's (ACHA) 100th anniversary, this article seeks to explore the second fifty years of its organizational history, as well as many of the key historical moments in the field of American college health. Materials and methods: This article examines ACHA's second fifty years, decade-by-decade, in key thematic areas that have driven focus, innovation and change at both ACHA and the field of college health and well-being, including: Changes in ACHA Governance, Leadership and Organizational Structure; Clinical Care, Immunizations, Emergency Preparedness and Outbreak Response; Health Promotion: Moving from Health to Wellness to WellBeing; Mental Health: Stigma, Suicide and Access to Care; Nursing Practice and Nurse Certification; Using Education, Research, Data and Publications to Drive Change and Innovation; Advocacy for the Health of College Students and Our College Communities; Growth and Development of the American College Health Foundation; and Recognizing Quality of Care, Excellence and Outstanding Contributions to ACHA. Results: ACHA's second fifty years have provided an enormous volume of high-quality programs and services, used to further improve the health and well-being of college students. The narrative shows that the organization has indeed met its mission over the past fifty years. The article concludes with predictions of changes and advances at ACHA in the next decade. Conclusions: Since 1920, ACHA has served as the voice for college student health and well-being in the United States. ACHA's second fifty years is a remarkable story of hard work, vision and achievement by a large number of talented and committed college health professionals, students and colleagues across college campuses and in sister professional organizations.