Huggins, who was born at Halifax in Nova Scotia, was educated at Acadia University and at the Harvard Medical School, where he obtained his MD in 1924. After graduate training at the University of Michigan he moved to the University of Chicago in 1927 where he has served as professor of surgery since 1936 and director of the May Laboratory of Cancer Research from 1951 until 1969.

In 1939 Huggins made a very simple inference that led to the development of new forms of cancer therapy. Noting that the prostate gland was under the control of androgens (male sex hormones) he concluded that cancer of the prostate might be treated by preventing the production of androgens. Admittedly his proposed treatment of orchiectomy (castration) might appear somewhat severe but it did lead to remissions in some cases and an alleviation of the condition in others.

Huggins soon appreciated however that the same results could probably be achieved by the less drastic procedure of the administration of female sex hormones to neutralize the effect of androgens produced by the testicles. Consequently in 1941 he began to inject his patients with the hormones stilbestrol and hexestrol. He was able to report later that of the first 20 patients so treated 4 were still alive after 12 years. Later workers, inspired by Huggins's work, treated women suffering from cancer of the breast with the male hormone testosterone and claimed improvement in some 20% of the cases.

It was for this work that Huggins shared the 1966 Nobel Prize for physiology or medicine with Peyton Rous.