The Marjoyoun National College was founded in 1946 on the initiative of Fadlo Hourani by a merger between the Greek Orthodox and Protestant schools. Fadlo, born in Jdeidet Marjeyoun in 1871, was inspired by his own education at the local Protestant school, and then at the American-founded elementary, secondary and university: the Syrian Protestant College of Beirut later renamed as the American University of Beirut.

The new school started to function in 1946 on the premises of the former Orthodox Bishopric with Qassis (Reverend) Hanna Hardan as principal and Chawki Haddad as vice-Principal. Its statutes defined it as a non-profit making, non-sectarian and co-educational institution, with a board of trustees and licenced as a public charity by the Lebanese government in April 1954.

In 1948 Labib Ghulmiyya succeeded as Principal, and under his dynamic leadership the school attracted day students and boarders from a wide area of Lebanon, and from Palestine, Syria, Iraq and Africa. Generous grants from the Ford Foundation and the American government enabled the trustees to build a campus of ten buildings on grounds purchased from resident and emigrant  owners through the efforts of Fadlo Hourani among Marjoyoun communities in North and South America. The new building was finished in 1962.

The civil strife in Lebanon which began in 1975 disrupted the functions of the school which closed temporarily in 1976, but re-opened in 1978. While Labib Ghulmiyya continued to support the school as much as was possible from war-torn Beirut, it re-opened in 1978 with Maurice Dabaghi as Principal.

Until the official end of civil war in Lebanon in 1990, the school operated under difficult and often dangerous times during Israeli occupation and resistance activities. Maurice Dabaghi, with a reduced but loyal staff of teachers and helpers, effectively ensured the survival of the school and the re-habilitation of its buildings. Until his retirement in 2014 he continued in this role to consolidate the school.

In 2014 the Board of Trustees appointed Imad Khoury as the new Principal.