While great emphasis has been placed on the role of social interactions as a driver of innovation growth, very few empirical studies have explicitly investigated the impact of social network structures on the innovation performance of cities. Past research has mostly explored scaling laws of socio-economic outputs of cities as determined by, for example, the single predictor of population. Here, by drawing on a publicly available dataset of the startup ecosystem, we build the first Workforce Mobility Network among metropolitan areas in the US. We found that node centrality computed on this network accounts for most of the variability observed in cities’ innovation performance and significantly outperforms other predictors such as population size or density, suggesting that policies and initiatives aiming at sustaining innovation processes might benefit from fostering professional networks alongside other economic or systemic incentives. As opposed to previous approaches powered by census data, our model can be updated in real-time upon open databases, opening up new opportunities both for researchers in a variety of disciplines to study urban economies in new ways, and for practitioners to design tools for monitoring such economies in real-time.