Europe has a long history as a global center of scientific research, but not all European regions are alike. Regions such as Île de France and the corridor that stretches from Cambridge to Oxford via London produce a disproportionate share of Europe’s science output. An econometric analysis sheds light on the factors that explain the spatial distribution of European science. One result is that the regional volume of Web of Science publications depends on the regional number of researchers in higher education institutions. This is however not the only cause of high output. Universities and their surrounding regions are slowly evolving institutional structures. Some regions host universities that are more than 500 years old. A second key result is that an increase in the age of a region’s oldest university is associated with greater output, other things being equal. Third, interregional accessibility via road, rail, and air networks is important for small regions, but not for large ones. Conversely, regional high-tech R&D employment is important for large but not for small regions.