Carl C. McIntire matriculated at Princeton Theological Seminary in 1927. In 1929, the seminary's curriculum was reorganized to encompass a variety of liberal theological views. Among other faculty members and some students, Professor of New Testament Literature John Gresham Machen resigned in protest and established the Westminster Theological Seminary of Philadelphia. McIntire, one of the group of students to leave Princeton, was one of the first to enroll at Westminster Seminary. He graduated in 1931 and was installed as pastor of the Chelsea Presbyterian Church, where he remained for two years. In 1933 he accepted a call from the Collingswood Presbyterian Church, NJ.

McIntire was one of a group of fundamentalists which repudiated the Board of Foreign Missions (PCUSA) and formed a rival Independent Board for Presbyterian Foreign Missions in 1934. The General Assembly promptly ordered all members of the Independent Board to sever their ties to it or to face disciplinary action. Refusing to obey the Assembly's mandate, McIntire was tried by a Special Judicial Commission of his presbytery in 1935 and found guilty of violating his ordination vows and defying the government of the PCUSA. In 1936, after a prolonged legal battle between the PCUSA and the Collingswood congregation, McIntire resigned from his church and was dismissed from the Presbyterian ministry.

Machen founded the Presbyterian Church of America, a fundamentalist church, in 1936. McIntire joined this church immediately. In 1941, he founded the American Council of Christian Churches and become its first president, and he went on from there to found and preside over the International Council of Christian Churches. He became a widely recognized public figure, speaking out against Communism, Roman Catholicism and integration.