Fritz Lejeune studied medicine, dentistry and comparative linguistics at the universities of Bonn and Greifswald. After his habilitation in 1922, he was appointed the same year as lecturer in the history of medicine at the University of Greifswald. Immediately after the First World War he was active within National Socialist and völkisch associations and states that he joined the NSDAP in 1923. In 1927 he was offered a lectureship in the history of medicine at the University of Cologne and a year later was appointed extraordinary professor there. In 1925 he co-founded and was chairman of the Reichsnotgemeinschaft Deutscher Ärzte. His involvement in National Socialist medical bureaucracy and, above all, his membership of numerous international medical history committees, made him a useful advocate for National Socialist foreign policy on behalf of the Propaganda Ministry. With his appointment as director of the Institute of the History of Medicine in Vienna, whose previous director Max Neuburger had been dismissed because of his Jewish origins, Lejeune reached the highpoint of his career. Thanks to Lejeune, the contents of the Institute's library – today's Zweigbibliothek für Geschichte der Medizin – were considerably enlarged between 1940 and 1945. The growth was a result of the generous financial subsidies from the Ministry of Internal and Cultural Affairs from 1940 but also through Lejeune's brazen acquisition of stocks from Viennese antiques dealers, which were involved in the booming Nazi book looting and Aryanizations. He obtained many items from Antiquariat Alfred Wolf, formed through the Aryanization and liquidation of antiques dealerships in 1938/39. Apart from his work at the Institute, Lejeune acted between 1940 and 1941 as a consultant and broker in the development of medical history libraries and as a supplier of books on medical history thanks to his contacts to Viennese antiques dealers. Thus he organized the incunabula from a medical history library for the pharmaceutical concern Boehringer & Sohn and the medical history literature for the Physiological Institute in Heidelberg. He worked particularly intensively with the Nazi leadership in Carinthia, especially Gauleiter Friedrich Rainer and his adviser Walter Medweth as part of the ostentatious Paracelsus commemoration organized by the National Socialist regime in Villach in 1941. In subsequent years he also collaborated in the development of a Paracelsus museum as the core of a planned medical history research institute.

After his flight from Vienna in early 1945, he was suspended by the dean of the Medical Faculty in Vienna on 10 May 1945. The Staatsamt für Volksaufklärung, für Unterricht und Erziehung und für Kultusangelegenheiten (State Office for Popular Enlightenment, Schools, Education and Cultural Affairs) dismissed Lejeune in June 1945. He was arrested by the US military and interned at the Glasenbach camp near Salzburg until the end of 1946 and then deported to Germany. His attempts to resume his university career in Germany were unsuccessful. In 1953 he was co-founder and long-standing chairman of Deutscher Kinderschutz to combat the supposed degeneration of West German youth through the adoption of a US lifestyle. In 1952 he was appointed a senator of the Deutsche Gesellschaft für Wissenschaft und Forschung and was closely involved in the founding of the Deutsche Angestellten-Krankenkasse health insurance company. From the mid‑1950s he was also active in the early anti-nuclear movement. He moved in 1965 to Villach, where he died a year later.