<p>Discussions on university–industry intermediaries are often presented as having their origin just after the Second World War, notably with the importance of the Bush Report (1945) and later the Bayh–Dole Act (1980). Very few studies have examined how science–industry intermediaries took form before that, even though the first forms of interaction between the “natural” and the “practical” can be traced back to the premises of modern science in the Renaissance. We thus propose an analysis of the emergence and evolution of science–industry intermediaries in the West from the Renaissance period to World War II. Using a neo-Schumpeterian evolutionary framework, the research highlights how intermediaries emerged and evolved to address changing challenges in science–industry relationships. The study reveals that early intermediaries (before the first Industrial Revolution) focused primarily on reducing transaction costs, while later periods (the first and second industrial ages) saw them take on broader responsibilities, such as facilitating knowledge transfer and addressing cultural divides, as science and industry became more institutionalized and separated. By analyzing various forms of intermediation, including patrons, exhibitions, academic and industrial societies, patent agents, etc., this work provides insights into the changing nature of science–industry relations and the complex and adaptive role of intermediaries.</p>