In May 1861, the Old School General Assembly passed the controversial Gardiner Spring Resolutions that called on Presbyterians to support the Federal Government of the United States as a religious duty.

A general assembly was scheduled to meet in Augusta, Georgia, on December 4, and by that time 47 presbyteries and 10 synods had severed ties to PCUSA.

The first General Assembly of the Southern Presbyterian Church accepted the recommendations of the convention and elected Benjamin M. Palmer its first moderator.

[9] The denomination grew during its early years in part due to the absorption of a number of smaller Presbyterian groups.

James Woodrow, professor at Columbia Theological Seminary, sparked controversy when he suggested that evolutionary thought did not contradict the biblical teachings on creation.

Despite his removal, Woodrow continued to be considered a member in good standing of the PCUS and was elected moderator of the South Carolina Synod in 1901.

[18][19] The response to the civil rights movement in effect split the PCUS into three factions: a liberal group desiring full endorsement of the movement's platform, a moderate faction desiring church-wide consensus before taking positive action, and a conservative/traditionalist group vigorously opposing what it believed was the meddling of the church in the civil and cultural traditions of its native region.

The conservative group strongly defended that teaching, but the liberal critics believed the doctrine was a justification for maintaining racial segregation and preserving the social standing of historic upper-class white elites within Southern society, a fair percentage of whom were PCUS members.

Having been eventually defeated numerous times in the General Assembly by a coalition of the liberals and moderates from the 1960s onward, some PCUS conservatives, primarily from non-metropolitan parts of the Deep South, founded what today is the Presbyterian Church in America (PCA) in late 1973.

They cited its rationale as "[a] long-developing theological liberalism which denied the deity of Jesus Christ and the inerrancy and authority of Scripture" on the part of PCUS leaders.

Some evangelicals, however, remained in the PCUS in order to contend for their beliefs; this group was more willing to perceive common cause with UPCUSA conservatives.

After the conservatives left the PCUS mainly for the PCA, but a minority for the EPC, it became easier for the remainder to work on union with the UPCUSA.

The PCUS was one of the more conservative bodies of Presbyterianism throughout most of its history, with a strong emphasis on subscription to the Westminster Confession and interest in Calvinist scholasticism, particularly as expressed in Common Sense Realism and later the Princeton Theology.