Before 1953 the Ford Foundation occupied executive offices in Pasadena, California and general offices at various locations throughout New York City. In the autumn of 1952, Treasurer Oliver May signed a lease for space in 477 Madison Avenue to unite the Foundation's New York operations within a single building and, early in the following year, a decision was made to relocate the executive offices to New York City. The combined Pasadena and New York staff consolidated into one office at 477 Madison Avenue in June 1954.

The Foundation continued to expand and, between 1958 and 1961, the Board of Trustees considered the possibility of moving to a larger building or transferring some of its staff to a separate building. In early 1963, the Board decided to construct a new building for the entire Foundation and engaged a realtor to locate the site. The site chosen was that of the former Grand Central Hospital at 321 East 42nd Street, originally built in 1912 for the Hospital for the Ruptured and Crippled (now the Hospital for Special Surgery). The Foundation appointed a Trustees' Building Committee on March 28-29, 1963, purchased the hospital grounds on April 1st, and took possession of the property on June 13th. A planning committee of six, responsible for the preparation of construction requirements and the selection of an architect, was formed shortly thereafter. The Ford Foundation selected the architectural firm Eero Saarinen and Associates (later known as Kevin Roche John Dinkeloo and Associates) to design the building. In July 1963, the Foundation purchased additional property to enable the lot to encompass a full rectangle. Turner Construction Company became the general contractor on July 30, 1963 and the Foundation signed a demolition contract with the Lipsett Division of Luria Brothers on August 6. The Luria Brothers completed the demolition of the hospital and a three-story apartment building in the northeast corner of the property in February 1964.

Preliminary site excavation began on May 1, 1964. In the same month, the Trustees' Building Committee approved the initial design for a 246,000 square foot building, exclusive of garden and terraces, with executive offices on the 11th floor and restaurant facilities on the 12th floor. In December, the Committee authorized the use of Cor-Ten weathering steel in lieu of reinforced concrete. The neighboring Hermitage apartment building threatened the Foundation with a lawsuit in November 1964 over the loss of access to light and air that would result from the new construction. The litigious parties settled out of court several months later.

Construction began in March 1965 with an initial budget of $22 million, and was completed less than two years later, but somewhat over budget. By June 1967 the estimated costs had risen to $25.5 million. The building was dedicated on December 8, 1967, although some floors had been occupied since September. In 1995, the American Institute of Architects and the American Architectural Foundation presented the Ford Foundation Headquarters Building with a Twenty Five Year Award given to buildings and structures that have "stood the test of time for 25 to 35 years" and that "[exemplify] design of enduring significance." Two years later, on October 21, 1997, the New York City Landmarks Preservation Commission awarded the building Landmark status.

Kevin Roche, the primary architect of the building, was recruited in 1950 by Eero Saarinen and Associates. By 1954, he had become the Principal Design Associate to Mr. Saarinen and assisted him on all projects until Mr. Saarinen's death in September 1961. In 1963 the Ford Foundation hired Eero Saarinen and Associates to design the new headquarters building at 320 E. 43nd Street. In 1966 Roche and his colleague, John Dinkeloo, changed the name of Eero Saarinen and Associates to Kevin Roche John Dinkeloo and Associates.

The Division of Administration oversaw the construction of the headquarters building and was tasked with building maintenance after construction. The Foundation formally established a Division of Administration in 1964 with responsibilities that grew to encompass the offices of the Vice President, Comptroller, and Personnel (added in 1966), Building Services (1967), Logistical Services (1968), and Program Related Investments (1969). In 1980, the Division of Organization and Management replaced the Division of Administration.

The Building Services Department was responsible for supervising the work of the contractors who provided food, operated and maintained the building; purchased, stored and distributed office supplies and equipment; printed and photocopied staff documents; purchased furniture and furnishings for the building; provided reception, telephone, and conference services; and ensured the building met fire, safety, and sanitation standards. Building services also maintained many of the construction records.

On December 10, 1964, Dr. Verne S. Atwater was asked by Ford Foundation President Henry T. Heald to assume overall responsibility for the planning and construction of the new building.

He earned a B.A. in 1942 from Heidelberg College, an MBA from Harvard Business School, and a PhD from New York University's School of Business in 1961, which he completed while attending classes at night. Following his graduation, Dr. Atwater served for two years as the Ford Foundation's first Representative in Latin America before being promoted to administrative Vice President and Director of the Latin America Program. By January 1965 he had reassigned his Latin American responsibilities to others in order to focus on administration. He resigned from the Foundation in May 1968 to become Chairman and CEO of the Central Savings Bank in New York. He later joined the faculty of Pace University, where he taught finance from 1982 to his retirement in 2002.

Rollin H. "R.H." McCarthy was the Director of Building Planning and Construction. He also worked with members of both the Foundation's management and the Trustees' Building Committee. He served as Director and ex officio on the Trustees' Building Committee from 1963 until he resigned in February 1, 1966 for health reasons.

Ralph G. Schwarz was the Director of Administrative Services. He replaced Mr. McCarthy as Director of Building Planning and Construction on February 1, 1966 and became an ex officio member of the Trustees' Building Committee.