Universities, medical centers, and headquarters are the driving forces behind cities’ innovation productivity and anchor-based urban revitalization efforts, such as innovation districts. As a result, there is increasing competition for corporate anchors, as well as emerging partnerships and conflicts. In each case, transit has a major role to play. Yet we know little about precisely how transit fits into the dynamics of anchor-based revitalization. To address this empirical gap, this study employed structural equation modeling to grasp both the direct and indirect impacts of transit on the knowledge-intensive firm location in 500 large U.S. cities. We conceptualized the indirect impact of transit as mediated by anchors with a composite value that we developed to quantitatively represent the presence and size of major innovation anchors in each city. According to our findings, the positive impact of transit on a city’s overall knowledge economy occurred through its role in supporting anchor institutions, a role that, in turn, significantly increased the likelihood of knowledge-based firms locating in the city. In short, transit quality was positively associated with larger and more established anchors, as well as the availability of more employees, which expands the city’s talent pool, a critical driver of knowledge-intensive employers’ location decisions. These findings call for greater attention to be paid to transit in cities’ anchor-based urban revitalization plans and to partnerships between cities, metropolitan organizations, and anchors in planning future transit systems.