Centered in the Midwestern United States, the denomination was made of German Protestant congregations of mixed Lutheran and Reformed heritage, reflecting the 1817 union of those traditions in Prussia (and other areas of Germany).

This union, both in Germany and in the United States, was deeply influenced by the pietist movement that was a reaction against centuries of scholasticism in Lutheran circles.

Generally speaking, in practice, ESNA clergy held to Calvinist views on baptism and Holy Communion (with a consequent de-emphasis upon European-style liturgy), while espousing Lutheran teachings such as justification by faith and the belief that law and gospel should be perceived differently, doctrines muted or even rejected in some other expressions of Calvinism throughout Europe and the U.S.

St. Johns Evangelical United Church of Christ (as it is known today) had been founded in 1838 by newly arrived German immigrants.

A memorial was erected in 1925 commemorating the founding of the Evangelical Synod of North America and still stands today in front of the church.

The oldest Evangelical Synod-heritage congregations are believed to be Femme Osage United Church of Christ near Augusta, Missouri; Bethlehem UCC in Ann Arbor, Michigan; Saint John's-Saint Luke Evangelical and Reformed UCC in Detroit, Michigan; or The United Church (UCC/United Methodist) in Washington, D.C., each of which were founded in 1833.