Rajewsky received his MD from the University of Frankfurt in 1962 and completed a fellowship at the Institut Pasteur in Paris. He joined the Institute for Genetics at the University of Cologne in 1964, where he remained until in 2001, and was head of its Department of Immunology. In 2001, he became the Fred S. Rosen Professor of Pediatrics and professor of pathology at Harvard Medical School before returning to Germany to establish the Immune Regulation and Cancer research group at the Max Delbrück Center for Molecular Medicine in 2011.

Rajewsky has greatly contributed to our understanding of normal and malignant development of antibody-forming cells, the mechanisms of somatic antibody diversification, and the formation of immunological memory. In the 1990s, Rajewsky and his colleagues developed conditional gene targeting, which enables specific genes of specific tissue in mice to be turned on or off—a technique that remains critical to understanding the function of genes and their role in the etiology of diseases. Rajewsky also identified B cells as the cells of origin for Hodgkin’s lymphoma. Most recently, his lab has focused on identifying signals mediating B-cell differentiation and survival, modeling of human B-cell lymphomas in mice, and analysis of microRNA control in the hematopoietic system.

Rajewsky has received international recognition for his work, including the Max Delbrück Medal, the Körber European Science Prize, the Max Planck Research Award, and Robert Koch Prize. He has also received an NIH Merit Award. Rajewsky is a member of the German National Academy of Sciences and a foreign member of the U.S. National Academy of Sciences, the American Academy of Arts and Sciences, and the Russian Academy of Sciences.