The central figure in the creation and operation of the Standard Oil Company during its rise to the top of the petroleum industry, John D. Rockefeller (JDR) established for the family a leading role in business and philanthropy. From the days of his earliest employment, Rockefeller, a devout Baptist, was generous in his giving to worthy causes, especially those of a religious nature. During the 1890s he developed an orderly system of philanthropic giving through an office staff that included his close advisor, Frederick T. Gates (1853-1929) and his son, John D. Rockefeller, Jr. (1874-1960). With the advice of these and other associates, Rockefeller established the University of Chicago, The Rockefeller Institute for Medical Research (now The Rockefeller University), the Rockefeller Foundation, and other philanthropic organizations working nationally and internationally in the fields of education, religion, and health. Rockefeller's total donations to philanthropic endeavors are estimated to have been $540 million.

John D. Rockefeller, Jr. (JDR Jr.) joined his father's office on October 1, 1897. He oversaw the expansion and diversification of the philanthropic work begun by his father. During his lifetime, the younger Rockefeller gave more than $537 million to educational, religious, cultural, medical, and other charitable projects.

John D. Rockefeller, Jr. and his wife, Abby Aldrich Rockefeller (1874-1948), passed the Rockefeller philanthropic impulse on to their children. Abby (1903-1976), John D. 3rd (1906-1978), Nelson A. (1908-1979), Laurance S. (1910-2004), Winthrop (1912-1973), and David (1915-2017) further expanded and diversified Rockefeller influence and interests, establishing their own philanthropic organizations, most notably the Rockefeller Brothers Fund (1940), and becoming more active politically.

The Office of the Messrs. Rockefeller was the name given the Rockefeller family office in the period following the Second World War, when John D. Rockefeller, Jr.'s sons returned from service to assume an increasing role in family business and philanthropic endeavors, even as they were pursuing their own careers and interests. The office provided family members with a range of services from routine office support (office space, staffing, purchasing, payroll and accounting, travel, security) to specialized investment and philanthropic advising, legal counsel, and a public relations staff.

To support their broad activity – a 1951 list of the family's associations detailed more than seventy organizations in which the five Rockefeller brothers actively participated in a business or philanthropic capacity – the family had long relied on a system of associates who worked with individual family members and provided specialized assistance and advice. The Rockefeller family office was originally located at 26 Broadway in the Standard Oil Building, but it moved to Rockefeller Center when the RCA Building opened in the fall of 1933. The family office occupied the 56th floor (and eventually the 54th and 55th floors) of the RCA Building, and was often known as Room 5600. Rockefeller philanthropies such as the American Conservation Association or the Rockefeller Brothers Fund also operated out of the family office space, and many affiliated businesses (such as Eastern Air Lines and eventually Rockresorts, Inc.) were neighboring Rockefeller Center tenants.