Hans Thacher Clarke was born in Harrow, England. He trained in organic chemistry at University College, London, and graduated in 1908 with a B.Sc. He then continued in research at University College until 1914, when he went to work for the Eastman Kodak Company, developing methods to synthesize many rare organic chemicals in short supply because of World War I. In 1928, Clarke became professor of biological chemistry and head of the department in the College of Physicians and Surgeons at Columbia University. He upgraded and expanded the department's experimental facilities, eventually developing a world-class facility. He was also known for welcoming foreign refugees and prominent scientists into his department. A major contribution of Clarke's department was the development of the isotopic tracer technique for the study of intermediary metabolism. He retired from Columbia in 1956 and took a position in the biochemical laboratory in the graduate school as a guest of Yale University. He remained there for nearly 8 years and then continued his work at the Children's Cancer Research Foundation in Boston.
Pursuing an early interest in the chemistry of organic compounds of sulfur, Clarke demonstrated the presence of a thiazole moiety in the structure of vitamin B1 and studied the formation of thiazolidine carboxylic acid from the reaction of cysteine and formaldehyde. This reaction became important in connection with the determination of the chemical structure of penicillin. Clarke also played a major administrative role in the United States–United Kingdom collaboration (1943–1946) to attempt the chemical synthesis of penicillin. In addition to his research, Clarke found time for other professional activities. He was a member of the editorial boards of Organic Syntheses and the Journal of Biological Chemistry and was associate editor of the Journal of the American Chemical Society. He was president of the Harvey Society in 1942 and president of the American Society of Biological Chemists from 1947 to 1948. Clarke was elected to the National Academy of Sciences in 1942 and received the Kings's Medal for service in 1948.