Over the last decade, a wealth of empirical evidence has accumulated describing the merits of team-based, collaborative, and interdisciplinary research, including: increased productivity among researchers, greater citation impact, increased multi-sector engagement, and the generation of novel solutions to grand challenges. Funding agencies have accordingly increased the frequency of large-scale collaborative and partnered grant opportunities. However, institutional structures and processes can inadvertently limit team-based interdisciplinary research at universities. Research Clusters (which we define as interdisciplinary networks of researchers who organize to solve key challenges facing society) provide a flexible and adaptable mechanism to enable collaborative research across internal and external institutional boundaries. Versions of research clusters are now commonly a central theme in research strategic plans at universities, but there remain very few resources available to research administrators and leadership to support the development of their internal strategies and processes to support research clusters. Here, we describe our experiences developing and implementing initiatives to catalyze clusters of research excellence at the institutional level and reflect on early successes and challenges. We share our framework for identifying, evaluating, and catalyzing research clusters and provide specific examples of internal processes and analytical tools that we have developed.