Born in Burlingame, Kansas, Sutherland was educated at Washington University, St. Louis. After serving in World War II as an army doctor he returned to St. Louis but in 1963 moved to Vanderbilt University, Tennessee, as professor of physiology. In the year before his death Sutherland joined the University of Miami Medical School in Florida.

In 1957 Sutherland discovered a molecule of great biological significance – 3,5–adenosine monophosphate, more familiarly known as cyclic AMP. At that time he was working with T. Rall on the way in which the hormone adrenaline (epinephrine) effects an increase in the amount of glucose in the blood. They found that the hormone stimulated the release of the enzyme adenyl cyclase into liver cells. This in turn converts adenosine triphosphate (ATP) into cyclic AMP, which then initiates the complex chain converting the glycogen stored in the liver into glucose in the blood. The significance of this reaction is that adrenaline does not act directly on the molecules in the liver cell; it apparently needs and ‘calls for’ what soon became described as a ‘second messenger’, cyclic AMP.

Sutherland went on to show that other hormones, such as insulin, also used cyclic AMP as a second messenger and that it was in fact used to control many processes of the cell. For his discovery of cyclic AMP Sutherland was awarded the 1971 Nobel Prize for physiology or medicine.