The mainline Protestant churches are a group of Protestant denominations in the United States and in some cases in Canada largely of the theologically liberal or theologically progressive persuasion that contrast in history and practice with the largely theologically conservative Evangelical, Fundamentalist, Charismatic, Confessional, Confessing Movement, historically Black church, and Global South Protestant denominations and congregations. Some make a distinction between "mainline" and "oldline", with the former referring only to denominational ties and the latter referring to church lineage, prestige and influence. However, this distinction has largely been lost to history and the terms are now nearly synonymous.

Protestantism is the largest grouping of Christians in the United States, with its combined denominations collectively comprising about 43% of the country's population in 2019. Other estimates suggest that 48.5% of the U.S. population is Protestant. Simultaneously, this corresponds to around 20% of the world's total Protestant population. The U.S. contains the largest Protestant population of any country in the world. Baptists comprise about one-third of American Protestants. The Southern Baptist Convention is the largest single Protestant denomination in the U.S., comprising one-tenth of American Protestants. Twelve of the original Thirteen Colonies were Protestant, with only Maryland having a sizable Catholic population due to Lord Baltimore's religious tolerance.