Stephen Harkness died when Edward was fourteen, leaving his wife and his oldest son, Charles, to manage the estate.

Henry was later the pastor of Madison Avenue Presbyterian Church, a few blocks away from Harkness and his wife's mansion in New York.

Harkness' mother gave the couple a new Italian Renaissance mansion on Manhattan's Upper East Side as a wedding present.

[9] Harkness' older brother Charles died in 1916 at age 55, leaving Edward more than US$80 million, $2.31 billion in 2024, much of it in Standard Oil stock.

CPMC was built in the 1920s on the site of Hilltop Park, the one-time home stadium of the New York Yankees, which Harkness purchased and donated.

Now known as NewYork-Presbyterian Hospital / Columbia University Medical Center, the Harkness Pavilion, named for father Stephen, is a central part of the campus.

[11] He also donated the Met's unofficial mascot, a blue decorative hippo from the Egyptian Middle Kingdom's Twelfth Dynasty that is known as "William".

Between 1926 and 1930, Harkness made major donations to his alma mater, Yale, and Harvard to establish residential college systems at each school.

[16] Around the same time as his Yale-Harvard philanthropy, Harkness sought to reform the pedagogical techniques of the country's elite boarding schools.

At Phillips Exeter Academy, he sought to innovate beyond rote learning by introducing the Harkness table method of instruction.

[18] He established the Harkness Fellowships and founded the Pilgrim Trust in the UK in 1930 with an endowment of just over two million pounds, "prompted by his admiration for what Great Britain had done in the 1914–18 war and, by his ties of affection for the land from which he drew his descent.

Edward and Mary Harkness are buried in Woodlawn Cemetery in The Bronx, New York City, which is today a National Historic Landmark.

[20] The Harkness family mausoleum is stately, designed to resemble a small medieval church, and includes a walled and locked private garden.

[21] In addition to the family-funded foundations, Harkness, along with another wealthy neighbor, Edward Crowninshield Hammond, was the inspiration for Eugene O'Neill's off-stage character "Harker", the "Standard Oil millionaire", in Long Day's Journey into Night, and on-stage figure "T. Stedman Harder" in A Moon for the Misbegotten.