Globalization is reshaping the relationship between U.S. universities and their host cities. U.S. universities must adjust to momentous changes in the worldwide higher education system, and U.S. cities must retool to maintain their place in the innovation economy. Institutional and civic resources are being pooled to form global-ready urban environments, giving rise to a new generation of urban settings. This article describes the historic cosmopolitan connection between cities and universities, discusses the global forces affecting that relationship today, and offers case illustrations of campus-oriented civic change in three U.S. localities. (Contains 4 figures.)