The earliest Christian church consisted of Jews in the first century who had known Jesus and heard his teachings. It gradually grew and spread from the Middle East to other parts of the world, though not without controversy and hardship among its supporters.

During the 4th century, after more than 300 years of persecution under various Roman emperors, the church became established as a political as well as a spiritual power under the Emperor Constantine. Theological and political disagreements, however, served to widen the rift between members of the eastern (Greek-speaking) and western (Latin-speaking) branches of the church. Eventually the western portions of Europe, came under the religious and political authority of the Roman Catholic Church. Eastern Europe and parts of Asia came under the authority of the Eastern Orthodox Church.

In western Europe, the authority of the Roman Catholic Church remained largely unquestioned until the Renaissance in the 15th century. The invention of the printing press in Germany around 1440 made it possible for common people to have access to printed materials including the Bible. This, in turn, enabled many to discover religious thinkers who had begun to question the authority of the Roman Catholic Church. One such figure, Martin Luther, a German priest and professor, started the movement known as the Protestant Reformation when he posted a list of 95 grievances against the Roman Catholic Church on a church door in Wittenburg, Germany in 1517. Some 20 years later, a French/Swiss theologian, John Calvin, further refined the reformers' new way of thinking about the nature of God and God's relationship with humanity in what came to be known as Reformed theology. John Knox, a Scotsman who studied with Calvin in Geneva, Switzerland, took Calvin's teachings back to Scotland. Other Reformed communities developed in England, Holland and France. The Presbyterian church traces its ancestry back primarily to Scotland and England.

Presbyterians have featured prominently in United States history. The Rev. Francis Mackemie, who arrived in the U.S. from Ireland in 1683, helped to organize the first American Presbytery at Philadelphia in 1706. One of the signers of the Declaration of Independence, the Rev. John Witherspoon, was a Presbyterian minister. The Rev. William Tennent founded a ministerial "log college" in New Jersey that evolved into Princeton University. Other Presbyterian ministers, such as the Rev. Jonathan Edwards and the Rev. Gilbert Tennent, were driving forces in the so-called "Great Awakening," a revivalist movement in the early 18th century.

The Presbyterian church in the United States has split and parts have reunited several times. Currently the largest group is the Presbyterian Church (U.S.A.), which has its national offices in Louisville, Ky. It was formed in 1983 as a result of reunion between the Presbyterian Church in the U.S. (PCUS), the so-called "southern branch," and the United Presbyterian Church in the U.S.A. (UPCUSA), the so-called "northern branch." Other Presbyterian churches in the United States include: the Presbyterian Church in America, the Cumberland Presbyterian Church and the Associate Reformed Presbyterian Church.