This paper provides a real world example of regional economic development theories in practice. Interdependencies between a major research university, a science/research park, an incubator, and a metropolitan area are presented to illustrate the effects on economic development, entrepreneurship, and innovation in the region. Narrating a trajectory of events of the past 50 years of developments in and around the University of Central Florida (UCF) campus, the case highlights the central role played by the university’s incubation program in catalysing the emergence of an extensive innovation infrastructure and enabling an entrepreneurial culture in Central Florida. Synthesising theory with practice, various challenges are discussed and lessons provided for policy makers, researchers and practitioners.