Charting significant growth in science production over the 20th century in four European Union member states, this neo-institutional analysis describes the development and current state of universities and research institutes that bolster Europe's position as a key region in global science. On-going internationalization and Europeanization of higher education and science has been accompanied by increasing competition as well as collaboration. Despite the policy goals to foster innovation and further expand research capacity, in cross-national and historical comparison neither the level of R&D investments nor country size accounts completely for the differential growth of scientific productivity. Based on a comprehensive historical database from 1900 to 2010, this analysis uncovers both stable and dynamic patterns of production and productivity in Germany, France, Belgium, and Luxembourg. Measured in peer-reviewed research articles collected in Thomson Reuters' Science Citation Index Expanded, which includes journals in the fields of Science, Technology, Engineering, Mathematics, and Health, we show the varying contributions of different organizational forms, especially research universities and research institutes. Comparing the institutionalization pathways that created the conditions necessary for continuous and strong growth in scientific productivity in the European center of global science emphasizes that the research university is the key organizational form across countries.