Originally established in 1924 for Italian-speaking immigrants, the church has adapted to serve the Turtle Bay neighborhood as well as the community associated with the nearby United Nations.

In November 1924, Cardinal Patrick Hayes decided to create a separate parish to serve the growing number of Italian immigrants in the area, which amounted to nearly 9,000 members.

Father De Nonno also began a tradition of holding a "motorists' mass" on Sunday afternoons to allow chauffeurs to attend after they finished driving passengers to morning worship services.

[11] A group of three paintings portraying the glorification of the Holy Family was dedicated on October 4, 1931, and blessed by Monsignor Michael J. Lavelle, rector of St. Patrick's Cathedral.

[14] St. Boniface Church, along with its parochial school hall that originally held masses for the Holy Family parish, were demolished in 1950 to create a parkway approach leading to the United Nations along the south side of East 47th Street between First and Second avenues (now part of Dag Hammarskjöld Plaza).

Sole, the project cost more than $2,225,000 and included a 142-foot (43 m) aluminum bell tower and a large windowless façade made up of granite panels with crosses intended to blend in with the United Nations and other buildings in the surrounding area.

The church complex also included a new rectory, an office and residence for the Permanent Observer of the Holy See to the United Nations, and the Pope John XXIII Pacem in Terris multilingual library.