Milton Friedman is usually presented as an economist characterized by his empirical approach to economics. His binary classification of economics into positive means and normative ends relies on the empirical content of predictions. Throughout his career, he used extensive, data-based statistical techniques. While important scholarly attention has been devoted to Friedman’s academic and political trajectories, his methodological prescriptions, and the development of economics at the University of Chicago, we know much less about the interplay of these elements. This paper proposes an intertwined reading of them. My aim is threefold. First, to understand Friedman’s work and methodological choices, I relate his empirical approach to his early training in statistics. Second, I articulate Friedman’s understanding of economics as an empirical policy science in the process of building the image of economists as neutral advisers in the policy-making process. Third, I claim that Friedman’s empirical methodological framework, developed while he was in the Economics Department of the University of Chicago, established the guidelines for an institutional long-term project that shaped it.