The synod's closed communion and its insistence on strict confessional agreement, the same commitments that let it organize in 1847, nearly split it apart again in the 1970s. Through the 1960s, professors at Concordia Seminary in St. Louis, the synod's flagship school, increasingly taught the Bible using the historical critical method, reading Scripture as a historically conditioned text open to the same critical tools scholars applied to any other ancient document, rather than the historical grammatical approach that treated it as the inerrant word of God. Many pastors and lay members in the pews saw that shift as a departure from the confession the synod had organized around in the first place.
The conflict came to a head on February 19, 1974, when synod president Jacob Preus suspended seminary president John Tietjen. Most of the faculty and student body walked out the same day rather than accept the suspension, regrouping under the name Concordia Seminary in Exile, Seminex for short, and holding classes on the campus of Saint Louis University, a Jesuit institution, while the dispute over who controlled the flagship seminary played out. Seminex operated from 1974 until 1987, affiliated for part of that span with the newly formed Association of Evangelical Lutheran Churches, a body that later folded into the Evangelical Lutheran Church in America, the LCMS's larger and more theologically liberal Lutheran counterpart. The walkout cost the LCMS a significant share of one generation's pastors and left the synod firmly on its confessional side of a divide that still separates it from the ELCA today.