This case study examines the application of PERMA (Seligman, 2011), positive organizational behavior (Luthans, 2002) and organizational culture change literature (Detert, Schroeder, Mauriel, 2000) to improve the health and well-being of faculty, staff, and students at an urban metropolitan university and its sister medical center campus. Driving this large-scale organizational change effort to prioritize wellness was the conviction that “siloed” and narrowly focused initiatives, replete with turf protection paranoia, would not be effective, sustainable or consistent with university system values. Establishing trust, inviting cross- collaborations, respecting disciplinary and role differences, and learning the unique contributions and hoped for outcomes of all stakeholders were critical steps in ensuring greater and more diverse engagement in promoting health and wellbeing. Examples of data-driven and collaboratively determined programs and initiatives to enhance wellbeing holistically by including physical, emotional, spiritual, intellectual, financial, environmental, physical, social, and occupational aspects of well-being will be discussed. Finally, we will share some lessons we learned as well as our future plans to continue to positively transform the culture to enhance full participation and improved well-being of all our stakeholders.