A graduate of Columbia University (Ph.D. 1910), Kendall joined the staff of the Mayo Foundation, Rochester, Minn., in 1914. His early research concerned the isolation of the active constituent (thyroxine) of the thyroid hormone. He also crystallized and established the chemical nature of glutathione, a compound important to biological oxidation-reduction reactions.

Kendall's most important research, however was the isolation from the adrenal cortex of the steroid hormone cortisone (which he originally called compound E; 1935). With Hench, he successfully applied the hormone in treatment of rheumatoid arthritis (1948). Kendall and Hench, along with Reichstein of Switzerland, received a Nobel Prize in 1950, and Kendall retired from his position as head of the biochemistry division of the Mayo Foundation in 1951. Kendall also acted as head of the biochemistry laboratory there from 1945 to 1951, and he was later visiting professor of chemistry at Princeton University.