Beginning in 1834 individual Presbyterian missionaries operating under the aegis of the American Board of Commissioners for Foreign Missions evangelized among Nestorian, Chaldean, and Jacobite communities in Mosul and Urumia. In 1870, the Presbyterian Church in the U.S.A. Board of Foreign Missions took over ABCFM work in Urumia and formed the West Persia Mission. Work around Mosul was taken over by the Church Missionary Society of the Church of England in 1900.

The United Mission in Mesopotamia was organized in 1924 as a joint effort of the Presbyterian Church in the U.S.A., the Reformed Church in America and the Reformed Church in the United States. In 1935, the name of the mission was changed to the United Mission in Iraq. Following denominational reorganizations in the 1950s and 1960s, the Reformed Church in America, the PCUS, the United Church of Christ and the UPCUSA constituted the Mission. The Mission was governed through a Joint Committee headquartered in New York.

The work of the United Mission centered around five stations, three of which were staffed by Presbyterian personnel. These included Mosul, the center of the old West Persia Mission; Hillah, occupied as an outstation in 1926 and elevated to full station status in 1930; and Dohuk, occupied in 1930. Work in Baghdad was directed by the Reformed Church in America, while the Reformed Church in the United States operated Kirkuk. The primary focus of the Mission's work was educational.

By 1930, all evangelical work in Iraq was part of the United Mission. The mission operated two schools: Baghdad High School Mansour, a school for girls in a western district of Baghdad; and the School of High Hope, a school for boys in Basra. Limits on the capacity of foreign missionary societies to operate schools or own land led the United Mission to vest operation of the schools in two other organizations: the American Philanthropic Society of Northern Iraq, which served as a board of trustees for Baghdad High School Mansour; and the American Philanthropic Society of Southern Iraq, which oversaw the School of High Hope. Further oversight and fundraising was undertaken by an organization of active and retired mission workers from Iraq, styled the Iraq Fellowship. In the 1960s, the United Mission in Iraq cooperated with the Committee on Cooperation in the Upper Nile, styled as the Joint Office for the Upper Nile and Iraq.

During the reign of King Faisal II and Nuri al-Said, Protestant work in Iraq proceeded without violence, with one prominent exception. In 1938, Roger Craig Cumberland, a Presbyterian evangelist in Dohuk, was murdered in his home by two Kurdish men for distributing Bibles. In the 1960s, the United Mission in Iraq established a fund for relief projects in Cumberland's name.

Following Gamal Abdel Nasser's success against the former colonial powers France and Great Britain in the 1956 Suez crisis, a wave of nationalist sentiment flooded the Middle East. Pressures on western-allied governments culminated in revolutions in Lebanon and Iraq in July 1958. The deposition of Faisal II, and the establishment of the Iraqi Republic marked the beginning of a period of struggle between factions of Arab nationalists, Iraqi nationalists, communists, and others. Following the 17 July 1968 coup d'etat, the Ba'ath Party came to power, and issued plans for nationalization of mission schools. After a year of uncertainty, schools were nationalized in the summer of 1969, and American mission workers were expelled. The United Mission in Iraq was dissolved in 1970.

Dedicated funds for work in Iraq still existed, however, in the Cumberland fund and in the general mission accounts. In 1979, a group of former mission workers in Iraq formed the Joint Committee for the United Mission in Iraq Interim Organization, with the apparent aim of identifying work to be supported in Iraq with these funds. The group persisted until at least 1988, at which point its funds were managed by the Presbyterian Foundation. 

Though a national evangelical denomination was never fully fledged in Iraq, the United Mission in Iraq supported the organization of congregations and the construction of Presbyterian churches in Kirkuk, Baghdad, and Mosul. The PC(USA) continues to connect the Iraqi churches with other Presbyterian churches in the region, such as the Evangelical Presbyterian Church of Egypt, the National Evangelical Synod of Syria and Lebanon, and the Reformed Church in Kuwait.