Harkness was born in Cleveland, Ohio, one of four sons of Anna M. Harkness and Stephen V. Harkness, a harness-maker who invested in and was one of the five founding partners in the forerunner of Standard Oil, John D. Rockefeller's oil company. Stephen Harkness died when Edward was fourteen, leaving his wife and oldest son, Charles, to manage the estate. Harkness attended St. Paul's School and Yale College, Class of 1897 and Columbia Law School. Harkness, his brother Charles, and cousin William were members of Wolf's Head Society at Yale. While at Yale, Ned enlisted the assistance of Henry Sloane Coffin as a tutor. Ned and Henry became friends and they roomed together at Yale. Henry later became the pastor of Madison Avenue Presbyterian Church just blocks away from Ned and Mary's home at 1 East 75th Street in New York. Also, Henry's brother William Sloane Coffin Sr. was the President of the Metropolitan Museum of Art from 1931–1933. Ned had already been heavily involved with the Metropolitan Museum of Art as a trustee and major donor and was likely instrumental in William Coffin's appointment.