He received his masters (A.M, 1936) in biology from Stanford University with a thesis entitled Some effects of thyroidectomy on the mammary glands and some other organs in the rat.

In the early years of his career at the Collis P. Huntington Memorial Laboratory at Harvard University, he became interested in clinical cancer research.

[4] Karnofsky is considered one of the pioneer medical oncologists, devoting his 30-year career to the successful use of chemotherapeutic agents to treat cancer.

[6] The primary purpose of the development of the scale was to allow physicians to evaluate a patient's ability to survive chemotherapy for cancer in a more objective manner.

When Karnofsky died of lung cancer in August 1969, a group of his friends donated a fund to be used to finance a yearly lecture at the annual meeting of the American Society of Clinical Oncology (ASCO).