Another major source of asset wealth was his art collection, ranging from impressionist to postmodern, which he developed through the influence upon him of his mother Abby and her establishment, with two associates, of the Museum of Modern Art in New York City in 1929. The collection, valued at several hundred million dollars, is scheduled for auction in Spring 2018, with proceeds to go to several designated nonprofit organizations, including Rockefeller University, Harvard University, the Museum of Modern Art, the Council on Foreign Relations, and the Maine Coast Heritage Trust.

In 1936, Rockefeller graduated cum laude from Harvard University. He also studied economics for a year at Harvard and then a year at the London School of Economics (LSE). At LSE he first met Future President John F. Kennedy (although he had earlier been his contemporary at Harvard) and once dated Kennedy's sister Kathleen. During his time abroad, Rockefeller briefly worked in the London branch of what was to become the Chase Manhattan Bank.

In 1940, Rockefeller married Margaret "Peggy" McGrath, who died in 1996. They had six children:

After completing his studies in Chicago, he became secretary to New York Mayor Fiorello La Guardia for eighteen months in a "dollar a year" public Service position. Although the mayor pointed out to the press that Rockefeller was only one of 60 interns in the city government, his working space was, in fact, the vacant office of the deputy mayor. From 1941 to 1942, Rockefeller was assistant regional Director of the United States Office of Defense, Health and Welfare Services.

Rockefeller enlisted in the U.S. Army and entered Officer Candidate School in 1943; he was ultimately promoted to Captain in 1945. During World War II he served in North Africa and France (he spoke fluent French) for military intelligence setting up political and economic intelligence units. For seven months he also served as an assistant military attaché at the American Embassy in Paris. During this period, he called on family contacts and Standard Oil executives for assistance.

In 1946, Rockefeller joined the staff of the longtime family-associated Chase National Bank. The chairman at that time was Rockefeller's uncle Winthrop W. Aldrich. The Chase Bank was primarily a wholesale bank, dealing with other prominent financial institutions and major corporate clients such as General Electric (which had, through its RCA affiliate, leased prominent space and become a crucial first tenant of Rockefeller Center in 1930). The bank also is closely associated with and has financed the oil industry, having longstanding connections with its board of Directors to the successor companies of Standard Oil, especially Exxon Mobil. Chase National became the Chase Manhattan Bank in 1955 and shifted significantly into consumer banking. It is now called J P Morgan Chase.

Rockefeller had a lifelong association with the Council on Foreign Relations (CFR) when he joined as a Director in 1949. In 1965, Rockefeller and other businessmen formed the Council of the Americas to stimulate and support economic integration in the Americas. In 1992, at a Council sponsored forum, Rockefeller proposed a "Western Hemisphere free trade area", which became the Free Trade Area of the Americas in a Miami summit in 1994. His and the Council's chief liaison to President Bill Clinton in order to garner support for this initiative was through Clinton's chief of staff, Mack McLarty, whose consultancy firm Kissinger McLarty Associates is a corporate member of the Council, while McLarty himself is on the board of Directors. He was also a trustee of the Carnegie Endowment for International Peace, including 1948, when Alger Hiss was President.

Rockefeller met Henry Kissinger in 1954, when Kissinger was appointed a Director of a seminal Council on Foreign Relations study group on nuclear weapons, of which David Rockefeller was a member. He named Kissinger to the board of trustees of the Rockefeller Brothers Fund, and consulted with him frequently, with the subjects including the Chase Bank's interests in Chile and the possibility of the election of Salvador Allende in 1970. Rockefeller supported his "opening of China" initiative in 1971 as it afforded banking opportunities for the Chase Bank.

Rockefeller started as an assistant manager in the foreign department. There he financed international trade in a number of commodities, such as coffee, sugar and metals. This position also maintained relationships with more than 1,000 correspondent banks throughout the world. He served in other positions and became President in 1960. He was both chairman and chief executive of Chase Manhattan from 1969 to 1980 and remained chairman until 1981. He was also, as recently as 1980, the single largest individual shareholder of the bank, holding 1.7% of its shares.

In 1964, along with other American Business figures such as Sol Linowitz, Rockefeller founded the non-profit International Executive Service Corps which encourages developing nations to promote private enterprise. In 1979, he formed the Partnership for New York City, a not-for-profit membership organization of New York businessmen. In 1992, he was selected as a leading member of the Russian-American Bankers Forum, an advisory group set up by the head of the Federal Reserve Bank of New York to advise Russia on the modernization of its banking system, with the full endorsement of President Boris Yeltsin.

In 1968, he declined an offer from his brother Nelson Rockefeller, then governor of New York, to appoint him to Robert F. Kennedy's Senate seat after Kennedy was assassinated in June 1968, a post Nelson also offered to their nephew John Davison "Jay" Rockefeller IV. President Jimmy Carter offered him the position of United States Secretary of the Treasury but he declined.

He was faulted for spending excessive amounts of time abroad, and during his tenure as CEO the bank had more troubled loans than any other major bank. Chase owned more New York City securities in the mid-1970s, when the city was nearing bankruptcy. A scandal erupted in 1974 when an audit found that losses from bond trading had been understated, and in 1975 the bank was branded a "problem bank" by the Federal Reserve.

Displeased with the refusal of Bilderberg Group meetings to include Japan, Rockefeller helped found the Trilateral Commission in July 1973.

From 1974 to 1976, Chase earnings fell 36 percent while those of its biggest rivals rose 12 to 31 percent. The bank's earnings more than doubled between 1976 and 1980, far outpacing its rival Citibank in return on assets. By 1981 the bank's finances were restored to full health.

In November 1979, while chairman of the Chase Bank, Rockefeller became embroiled in an international incident when he and Henry Kissinger, along with John J. McCloy and Rockefeller aides, persuaded President Jimmy Carter through the United States Department of State to admit the Shah of Iran, Mohammad Reza Pahlavi, into the United States for hospital treatment for lymphoma. This action directly precipitated what is known as the Iran hostage crisis and placed Rockefeller under intense media scrutiny (particularly from The New York Times) for the first time in his public life.

In the 1980s, Rockefeller became embroiled in controversy over the mortgaging and sale of Rockefeller Center to Japanese interests. In 1985, the Rockefeller family mortgaged the property for $1.3 billion, with $300 million of that going to the family. In 1989, 51 percent of the property, later increased to 80 percent, was sold to Mitsubishi Estate Company of Japan. This action was criticized for surrendering a major U.S. landmark to foreign interests. In 2000, Rockefeller presided over the final sale of Rockefeller Center to Tishman Speyer Properties, along with the Crown family of Chicago, which ended the more than 70 years of direct family financial association with Rockefeller Center.

Rockefeller retired from active management of the bank in 1981, succeeded by his protégé Willard C. Butcher. Former Chase chairman John J. McCloy said at the time that he did not believe that Rockefeller would not go down in history as a great banker but as a "real personality, as a distinguished and loyal member of the community".

He published Memoirs in 2002, the only time a member of the Rockefeller family has written an autobiography.

In 2005 he gave $100 million to the Museum of Modern Art and $100 million to Rockefeller University, two of the most prominent family institutions; as well as $10 million to Harvard and $5 million to Colonial Williamsburg. In 2006, he pledged $225 million to the Rockefeller Brothers Fund upon his death, the largest gift in the Fund's history. The money will be used to create the David Rockefeller Global Development Fund, to support projects that improve access to health care, conduct research on international Finance and trade, fight poverty, and support sustainable development, as well as to a program that fosters dialogue between Muslim and Western nations. Rockefeller donated $100 million to Harvard University in 2008. The New York Times estimated in November 2006 that his total charitable donations amount to $900 million over his lifetime, a figure that was substantiated by a monograph on the family's overall benefactions, entitled The Chronicle of Philanthropy.

Though a lifelong Republican and party contributor, he was a member of the moderate "Rockefeller Republicans" that arose out of the political ambitions and public policy stance of his brother Nelson. In 2006 he teamed up with former Goldman Sachs executives and others to form a fund-raising group based in Washington, Republicans Who Care, that supported moderate Republican candidates over more ideological contenders.

Rockefeller was born in New York City, New York. He grew up in an eight-story house at 10 West 54th Street, the tallest private residence ever built in the city. Rockefeller was the youngest of six children born to financier John Davison Rockefeller Jr. and socialite Abigail Greene "Abby" Aldrich. John Jr. was the only son of Standard Oil co-founder John Davison Rockefeller Sr. and schoolteacher Laura Celestia "Cettie" Spelman. Abby was a daughter of Senator Nelson Wilmarth Aldrich and Abigail Pearce Truman "Abby" Chapman. David's five elder siblings were Abby, John III, Nelson, Laurance, and Winthrop.

Rockefeller attended the experimental Lincoln School at 123rd Street in Harlem.

The Kykuit section of the Rockefeller family compound is the location of The Pocantico Conference Center of the Rockefeller Brothers Fund (RBF) – set up by David and his four brothers in 1940 – which was created when the Fund leased the area from the National Trust for Historic Preservation in 1991.

Rockefeller was acquainted with Central Intelligence Agency (CIA) Director Allen Dulles and his brother, Eisenhower administration Secretary of State John Foster Dulles—who was an in-law of the family—since his college years. It was in Rockefeller Center that Allen Dulles had set up his WWII operational center after Pearl Harbor, liaising closely with the MI6, which also had their principal U.S. operation in the Center. He also knew and associated with the former CIA Director Richard Helms, as well as Archibald Bulloch Roosevelt Jr., a Chase Bank employee and former CIA agent whose first cousin CIA agent Kermit Roosevelt Jr. was involved in the Iran coup of 1953. Also, in 1953, he had befriended william Bundy, a pivotal CIA analyst for nine years in the 1950s, who became the Agency liaison to the National Security Council, and a subsequent lifelong friend. Moreover, in Cary Reich's biography of his brother Nelson, a former CIA agent states that David was extensively briefed on covert intelligence operations by himself and other Agency division chiefs, under the direction of David's "friend and confidant", CIA Director Allen Dulles.

Rockefeller's principal residence was at "Hudson Pines", on the family estate in Pocantico Hills, New York. He also had a Manhattan residence at 146 East 65th Street, as well as a country residence (known as "Four Winds") at a farm in Livingston, New York (Columbia County), where his wife raised Simmenthal beef cattle. He also maintained a summer home "Ringing Point" at Seal Harbor on Mount Desert Island off the Maine coast. In May 2015, he donated one thousand acres of land in Seal Harbor to the Mount Desert Land and Garden Preserve.

Rockefeller died in his sleep from congestive heart failure on March 20, 2017 at the age of 101 at his home in Pocantico Hills, New York.