At the age of 14 at a communion service at Rogart, Scotland, Mackay had a profound religious experience that influenced the remainder of his life.
When he was graduated in 1915, he won a fellowship in didactic and polemic theology, which he used toward studies in Spanish culture at Madrid, Spain, to prepare for missionary work in Latin America.
From his position as school master, Mackay entered intellectual circles and became a member of a literary group that included Victor Andres Belaunde, Professor of Philosophy at San Marcos University.
From April to July 1930 Mackay and his family lived in Bonn, Germany where he attended the lectures of Karl Barth and began a friendship with him.
In 1936, Mackay reluctantly left the foreign mission field to become the third president of Princeton Theological Seminary which had recently been weakened by the secession of several professors, including his own former teacher, J. Gresham Machen.
For the next 24 years as both president and professor of ecumenics, Mackay worked on many fronts to revive the institution's health, inspiring it to evangelical dynamism and leaving it on a sound footing, with expanded faculty, student body, and campus plant.
After retirement from the seminary, he served from 1961 to 1964 as adjunct professor of Hispanic thought at American University, Washington, D.C. An eloquent and charismatic platform speaker and preacher, Mackay was often called upon to present keynote addresses at conferences, assemblies, and gatherings.
In addition to writing the influential "Letter to Presbyterians", which fortified resistance to McCarthyism in the United States, Mackay was also the primary draftsman of a number of other church statements and messages on behalf of various ecclesiastical councils and conferences.
Thus, as a fellow Presbyterian leader correctly concluded, Mackay exerted influential leadership in three broad areas: Missions, the Ecumenical Movement, and social and political thought and action.
He believed in a personal and incarnational approach to foreign missions by which the missionary would become a member of the community and earn the right to be heard through particular service that met specific needs within the receiving culture.
"[12] In 1964 in Lima, Mackay was presented with the Palmas Magisteriales, a civic honor and the highest government award for educational services to Peru.
In his final years Mackay moved to a Presbyterian retirement community in Hightstown, New Jersey, and died early on June 9, 1983.