Colleges and universities in the United States have faced extraordinary pressures in the past ten years due to economic strains, political challenges, and demographic shifts. These stressors on institutional viability have pushed some state systems of higher education and politicians to increasingly consider mergers as a strategy to reduce costs and increase educational attainment levels and meet workforce needs. However, the implementation of mergers remains an unusual and understudied change initiative. Using an embedded, single-case study methodology, this study expands on Tierney’s (1988b, 2008) theoretical framework related to organizational culture in American higher education while drawing upon organizational communication theory and sensemaking theory to explore the overarching questions of how organizational cultures shape the merger process and change as a result of the process. Combining research on higher education mergers, organizational culture and communication, and sensemaking with interviews of institutional leaders and an analysis of relevant documents, this study provided a unique examination of the role of institutional culture and communication in higher education mergers. Significant findings emerging from the study underscored the disruptive nature of mergers and the importance of robust communication strategies to help stakeholders understand the need for the change and reduce the level of uncertainty associated with change, engage stakeholders in the change implementation process, and envision future opportunities. The study also confirmed that, despite similarities among institutions of higher education, each campus has a unique culture that reflects its mission, leadership, customs, socialization, and ways of making decisions. These distinctive cultural elements have significant influence during the merger process, as community members make sense of the changing organizational structure.