Clarkes father had been the European representative of US photographic pioneer company Kodak for several years, and was a personal friend of founder George Eastman. After Hans graduated in Chemistry, Eastman consulted with him a few times regarding chemistry-related processes. When World War I erupted, Eastman was forced to look for other sources of the chemicals that he had been obtaining from Germany, and he turned to Hans Clarke for assistance. At Eastmans request, Clarke moved to Rochester, New York in 1914 to assist what he assumed to be the company's considerable chemical engineering department. He was shocked to discover that he was the sole organic chemist there.
Clarke stayed with Kodak until 1928, when he was invited to become the Professor of Biological Chemistry in the Columbia University College of Physicians and Surgeons. His administrative skills and ability to recognize talent contributed to the growth of Columbia's biochemistry department, which by the 1940s had become one of the largest and most influential in the United States.
As the dark events foreshadowing World War II pushed eminent Jewish scientists out of Europe, Clarke opened his laboratory to refugee biochemists, among them E. Brand, Erwin Chargaff, Zacharias Dische, K. Meyer, David Nachmansohn, Rudolph Schoenheimer, and Heinrich Waelsch.
As head of Columbia's Biochemistry Department, Clarke took a personal interest in graduate students, of whom he demanded rigorous qualifications prior to admission. As time went on he devoted less time to his own research, becoming inundated with departmental and professional responsibilities.
Clarke's time at Kodak resulted in few publications in the chemical literature, but he aided the preparation of 26 substances to the Organic Syntheses series, and checked some 65 others. He stayed associated with Kodak for the rest of his life, only retiring as a consultant in 1969. Among other researches, he was involved in the production of penicillin in the United States.
Clarke retired from Columbia in 1956 due to its mandatory retirement policy, but was able to move to Yale University, where he spent eight years in full-time research. When Yale required the space that he was occupying he moved again, and did another seven years work at the Childrens Cancer Relief Foundation in Boston, Massachusetts.