In 1922, Schlick became a professor in the philosophy of inductive sciences at the University of Vienna after two unsatisfying appointments in Rostock and Kiel. In the same year occurred two events that shaped the remainder of Schlick's life. First, a group of philosophers and scientists (including but not limited to Rudolf Carnap, Herbert Feigl, Kurt Gödel, Hans Hahn, Otto Neurath, and Friedrich Waismann) suggested to Schlick that they conduct regular meetings to discuss science and philosophy. They initially called themselves the Ernst Mach Association, but forever after they have been known as the Vienna Circle. The second great event of 1922 was the publication of Ludwig Wittgenstein's Tractatus Logico-Philosophicus, a work of terse, lapidary brilliance that advanced, among other things, a logical theory of symbolism and a 'picture theory' of language. Schlick and his group were overwhelmed by the work: they made it a topic for discussion at nearly every meeting. Schlick himself contacted Wittgenstein in 1924 and extolled the virtues of Wittgenstein's book vis-a-vis his immediate circle. Eventually Wittgenstein agreed to meet with Schlick and Waismann to discuss the Tractatus and other ideas. Through Schlick's influence, Wittgenstein was encouraged to consider a return to philosophy after some ten years of idleness. It is partly to Schlick's credit that Wittgenstein began to pen the reflections that make up large parts of Philosophical Investigations. Schlick and Waismann's discussions with Wittgenstein continued until the latter felt that germinal ideas had been used without permission in an essay by Carnap. Wittgenstein continued discussions in letters to Schlick, but his formal association with the Vienna Circle ended in 1932.
Schlick had worked on his "General Theory of Knowledge" between 1918 and 1925, and, though later developments in his philosophy were to make various of his epistemological contentions untenable, the "General Theory" is perhaps his greatest work in its acute reasoning against synthetic a priori knowledge. Between 1926 and 1930, Schlick labored to finish "Problems of Ethics," in which he surprised some of his fellow Circlists by including ethics as a viable branch of philosophy. Also during this time, the Vienna Circle published "The Scientific View of the World: The Vienna Circle" as an homage to Schlick. Its strong anti-metaphysical stance crystallized the viewpoint of the group.
With the rise of the Nazis in Germany and Austria, many of the Vienna Circle's members left for America and Great Britain. Schlick, however, stayed on at the University of Vienna: when visited by Herbert Feigl in 1935, he expressed dismay at events in Germany. In June 1936, Schlick was ascending the steps of the University for a class when he was confronted by a former student who harangued him about an essay he had written. When Schlick demurred, the student drew a pistol and shot Schlick in the chest. He died very soon afterward. The student was tried and sentenced, but his became a cause celebre for the growing racist sentiments in the city, and he was popularly portrayed as a "heroic Aryan" rising up against the "soulless Jewish philosophy" of the Circle. (That Schlick was not Jewish tended to be overlooked by these same people.) In a fitting and grotesque twist of fate, the student was paroled shortly afterward and became a member of the Austrian Nazi Party after the Anschluss.
Schlick's enduring contribution to the world of philosophy is as the fount of logical positivism. His humanity, good will, gentleness, and especially his encouragement have been documented by many of his peers. Herbert Feigl and Albert Blumberg, in their excellent introduction to "General Theory of Knowledge," have written, "No other thinker was so well prepared to give new impetus to the philosophical questings of the younger generation. Though many of his students and successors have attained a higher degree of exactitude and adequacy in their logical analyses of problems in the theory of knowledge, Schlick had an unsurpassed sense for what is essential in philosophical issues." (Feigl and Blumberg, "Introduction," "General Theory of Knowledge," p. xxi).