It was at this formative stage that he began to develop the "falsifiability" doctrine that has made him one of the most important philosophers of science. Popper came to understand that Einstein's theory contained a critical spirit which was absent from the theories of Marx and Freud. Einstein's theory had implications which could be tested and, if proved false, would have falsified the theory itself. The theories of Marx and Freud, by contrast, though claiming to be "scientific", were essentially untestable.

Popper worked as a school teacher before taking his PhD in philosophy at the University of Vienna in 1928. The dominant school of philosophy at that time - the so-called Vienna Circle - sought to remove metaphysics from philosophy by applying a "scientific" verification principle to language. Popper sympathised with the scientific attitude of these so-called logical positivists, but criticised their theory of verification in scientific methodology. In The Logic of Scientific Discovery (1934, translated in 1959), he proposed his famous criterion of testability, or falsifiability, for scientific validity. This characterisation of the scientific method was Popper's most significant contribution to the philosophy of science.

Popper's book made his reputation as a philosopher and in 1935 he was invited to lecture in England. The growth of Nazism forced him from Austria and from 1937-45, he taught at Canterbury University, New Zealand. The Nazi takeover of Austria in 1938 led him to consider questions of social and political philosophy and his passionate defence of democratic liberalism was expressed in two classics, The Poverty of Historicism (1944) and The Open Society and Its Enemies (1946). In these, he demolished the notion of historical determinism and exposed the totalitarian implications of the political theories of Plato and Karl Marx.