Born in Cleveland, Ohio, one of three children born to Anna Richardson and her husband Stephen V. Harkness, a harnessmaker who invested with John D. Rockefeller, becoming the second-largest shareholder in Standard Oil.
He attended Yale University, Class of 1897.
His father Stephen V. Harkness died in 1888.
His elder brother Charles W. Harkness died in 1916, and in 1917 Anna Harkness gave $3,000,000 to Yale University to build Harkness Quadrangle in his memory.
In 1918 Anna Harkness established the Commonwealth Fund by a gift of $20,000,000, and Edward Harkness became its president.
Edward Harkness married Mary Stillmann, whose family had also been associated with the Rockefellers.
Through his philanthropy, he built most of the undergraduate dorms at Harvard University and Yale University.
The Commonwealth Fund helped build Columbia University's College of Physicians and Surgeons.