Willem J. Kolff was born on 14 February 1911 in Leyden, Holland. His father, Jacob Kolff, was director of the Tuberculosis Sanatorium at Beekbergen, where Kolff spent a great deal of his childhood. Kolff graduated from the Leyden Medical School in 1938, and in 1946 received a Ph.D. summa cum laude from the University of Groningen. During the German occupation of the Netherlands in 1941, he developed the first practical artificial kidney in the ancient town of Kampen, with materials scrounged from a local factory and carefully concealed from the Nazis. In September 1945 the device saved its first patient.

Kolff and his family immigrated to Cleveland, Ohio, in 1950, where he became head of the department of artificial organs and professor of clinical investigation at the Cleveland Clinic Foundation. There he began work on an artificial heart, and in 1957 the implantation of a totally artificial heart in the chest of an animal was accomplished for the first time. Kolff left Cleveland in 1967 to continue his work on the artificial heart. He arrived at the University of Utah and became director of the Institute for Biomedical Engineering and its artificial organs division. Under Kolff's leadership, the University of Utah has since developed one of the world's leading artificial organ research centers. In 1982, under his supervision, the first fully artificial heart was implanted in a human patient, Barney Clark. Kolff retired in 1986 on his 75th birthday but continues to work part-time.

Kolff's accomplishments have been honored with many awards for his efforts in the study and research of artificial organs. These include the Amory Prize in 1947, the designation as one of the nation's top ten physicians in 1964, the Valentine Medal and Award in 1969 for his "outstanding contributions to the field of urology." He joined Lister, Pasteur, and other medical greats in 1964 when he was named winner of the Cameron Prize for Practical Therapeutics by the University of Edinburgh. Perhaps his most impressive award was the rank of Commander in the Order of Oranje-Nassau by Queen Juliana of the Netherlands. It was the first time the award had been presented to an individual living in the United States, and is the highest tribute for accomplishment in the field of science which can be conferred by the government of the Netherlands upon a native of that country. Kolff has also published large array of medical articles; more than 300 articles in scientific journals bear his name.