Klaproth was an apothecary for many years, but his own study of chemistry enabled him to obtain a post as pharmaceutical assessor in a medical school in Berlin in 1782. He began teaching chemistry at various military and other schools, and he was chosen to be professor of chemistry at the newly founded University of Berlin in 1810.

The leading chemist of his time in Germany, Klaproth was an exact and conscientious worker who helped to improve and systematize analytic chemistry and mineralogy. He was one of the earliest non-French adherents of Antoine Lavoisier's antiphlogistic doctrines. He rediscovered titanium (1795) about four years after its initial discovery and named it. He elucidated the composition of many substances, including compounds of tellurium, strontium, beryllium, and chromium. In addition to more than 200 papers, he published a five-volume chemical dictionary with F.B. Wolff (1807–10) and a four-volume supplement (1815–19).