Between 1913 and 1915, he worked in the William Henry Howell's lab at Johns Hopkins School of Medicine, studying blood thinning proteins, such as antithrombin.

In 1915, he secured a junior position on the medical staff of the Massachusetts General Hospital, where he started research on blood anemia.

As part of those duties, he worked with Alice Hamilton to understand what was causing workers at a munitions plant in New Jersey to become ill.

In addition, Minot became professor of medicine at the Harvard University, and was appointed director of the Thorndik Memorial Laboratory at Boston City Hospital.

He was a member of the Pernicious Anemia Committee at Harvard and served on the Anti-Anemia Preparation Advisory Board of the U.S.

Minot shared the 1934 Nobel Prize in Physiology or Medicine with William P. Murphy and George H. Whipple given for their work on the treatment of blood anemia.

[11] Minot and Murphy's famous paper Treatment of pernicious anemia by a special diet was published in 1926.