Clarke was elected to the National Academy of Sciences in 1942, and served on the boards of the Journal of the American Chemical Society and of the Journal of Biological Chemistry. He was a member of the American Philosophical Society, the American Chemical Society, the American Otological Society, and the American Society of Biological Chemists. He is probably best known for his work on the eponymously named Eschweiler-Clarke reaction. In 1973 his widow donated his voluminous personal and research papers to the American Philosophical Society.
Clarke was named Assistant Director of the Office of Scientific Research and Development in 1944, which placed him in charge of coordinating penicillin production in the United States.
Clarke served as Science attaché to the US Embassy in London (1951–52). He was able to work closely with Sir Robert Robinson, with whom he had edited a major book on research in penicillin (issued in 1949).
Clarke was chairman of the Rochester section of the American Chemical Society (1921), of the New York section (1946) and of the Organic Chemistry Division (1924–25). He worked on the Committee on Professional Training, and the Garvin Award Committee. He was a president of the American Society of Biological Chemists (1947). He served on several grant-allocating committees. As a member of the Otological Society he served on a grants committee from 1956 to 1962. He was Chairman of the Merck Fellowship Board of the National Academy of Sciences in 1957.
Clarke was much in demand for his talents as a lucid writer and was called on to serve as editor or referee throughout his career. He sat on the editorial board of Organic Syntheses (1921–32), and on the editorial board of the Journal of Biological Chemistry (1937–51), and was associate editor of the Journal of the American Chemical Society (1928–38)
Clarke was an expert clarinet player, and received numerous requests to perform. His donated papers include one notebook dedicated to clarinet performance.