D'Escoto felt called to serve as priest and entered the seminary of the Maryknoll Missionary Society in 1953. He was ordained a priest of the Society in 1961 before becoming engaged in politics. He earned a Master of Science degree from the Columbia University Graduate School of Journalism the following year, and was a key figure in the founding of the Maryknoll publishing house, Orbis Books, in 1970. He served as an official of the World Council of Churches. As an adherent of liberation theology, he secretly joined the Sandinistas. D'Escoto formed the Nicaraguan Foundation for Integral Community Development (FUNDECI) in January 1973 to promote a nongovernmental response to the displacement of thousands in the December 1972 Managua earthquake. He continued on as President of FUNDECI, which operates in several departments in Nicaragua until his death in 2017.