Koshland's private fortune, derived from Levi Strauss put him on lists of America's wealthiest men. His early work was in enzyme kinetics at Brookhaven National Laboratory, Long Island, and Rockefeller University, New York. This led him to propose the induced fit model for enzyme catalysis. After this advance, he turned to studying the how bacteria control their movements in chemotaxis.
As chairman of the biochemistry department at the University of California at Berkeley he reorganized the department, streamlining it along modern lines into three departments, of cell and molecular biology, integrative biology and the biology of microbes and plants.