George Richards Minot was born in Boston, Massachusetts to James Jackson Minot (1853–1938) and Elizabeth Whitney. He was namesake of his great-great-grandfather George Richards Minot (1758–1802). His father was a physician; his father's cousin was Anatomist Charles Sedgwick Minot (1852–1914); one of his great-grandfathers was James Jackson (1777–1867), co-founder of Massachusetts General Hospital. He developed interest, first, in the natural sciences, and then, in Medicine.

Minot and his wife Marian Linzee Minot (Weld) (1890-1979), whom he married in 1915, had two daughters and a son.

Minot completed his B.A. in 1908, and obtained his M.D. degree in 1912 from the Harvard Medical School. Between 1913 and 1915, he worked in the william Henry Howell's lab at the Johns Hopkins Medical School in Baltimore, MD., 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. During the first world war, he served as a surgeon in for the US Army. 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. They eventually discovered that skin contact with TNT led to the sicknesses.

In 1917, he came to Collis P. Huntington Memorial Hospital in Boston; he became chief of medical services in 1923, and was appointed physician-in-chief in 1934. 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 also worked in the Peter Bent Brigham Hospital as a staff member. He was a member of the Pernicious Anemia Committee at Harvard and served on the Anti-Anemia Preparation Advisory Board of the U.S. Pharmacopoeia.

However, insulin was discovered at about the same time Minot was diagnosed. Insulin became widely available about a year later. Dr. william Castle observed that Frederick Banting's and Charles Best's discovery of insulin in 1921, not only transformed diabetes treatment, but also, by keeping Minot alive, contributed towards the discovery of a cure for pernicious anemia.

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. They all discovered an effective treatment for pernicious anemia, which was a terminal disease at the time, with liver concentrate high in vitamin B₁₂, later identified as the critical compound in the treatment.

Minot began developing complications associated with diabetes in 1940, and suffered a serious stroke in 1947, which partially paralyzed him. He died in Brookline, Massachusetts on February 25, 1950. He was a Unitarian. His home in Brookline, Massachusetts, was designated a National Historic Landmark in recognition for his work.