Clausius was appointed professor of physics at the Artillery and Engineering School at Berlin in 1850, the same year in which he presented a paper stating the second law of thermodynamics in the well-known form: “Heat cannot of itself pass from a colder to a hotter body.” He applied his results to an exhaustive development of the theory of the steam engine, stressing the concept of entropy (dissipation of available energy). He became professor of physics at Zürich Polytechnikum in 1855, and, two years later, contributed to the theory of electrolysis (the breaking down of a compound by electricity) by suggesting that molecules are made up of continually interchanging atoms and that electric force does not cause but simply directs the interchange. This view later was used as the basis of the theory of electrolytic dissociation (breakdown of molecules into charged atoms or ions).

He became professor of physics at the University of Würzburg in 1867 and at the University of Bonn in 1869. In molecular physics, Clausius restated the French physicist Sadi Carnot's principle concerning efficiency of heat engines and thus provided a much sounder basis for the theory of heat.