In his roles as a denominational executive, international ecclesiastical figure, and academic leader, Horton strongly advocated efforts undertaken by churches to unite organizationally with each other, even those of unlike theological and governmental persuasion.
He demonstrated a peculiar desire to, in the "Faith and Order" components of world ecumenical discussion, advance the notion that God desired for those Protestant churches separated for generations due to minor conflicts over theology and, more speciously, ethnic and socioeconomic differences to overcome the alienations of the past and join forces to bring a stronger Christian witness to a world beset by wars, poverty, and increasing indifference or hostility toward spiritual matters.
Due to his acumen and the keen ecumenical leanings of the CC Churches, Horton became the denomination's minister and general secretary in 1938, which gave him the leadership of the main national decision-making entity within the group.
This enabled the final stages of the merger process to proceed, to the point of the actual union on June 25, 1957; the merged body took the name United Church of Christ.
At Harvard, Horton expanded upon his inter-church interests, bringing new programs to the school such as religious studies and a chair in Roman Catholic theology.