With the encouragement of Henry Melchior Muhlenberg (1711–1787), the Ministerium was founded at a Church Conference of Lutheran clergy on August 26, 1748.

They were particularly attracted by William Penn's promise of religious freedom in what was then the colonial Province of Pennsylvania and came to the Philadelphia region in significant numbers.

A conference was proposed to create a closer union between the area congregations' preachers, elders, and deacons.

A tension between pious and orthodox religious interpretations was present in Europe and North American Lutherans.

Six pastors and lay representatives from ten congregations attended the meeting, where they agreed to work together as the "ministerium of North America."

[7] Attendees came from Philadelphia, New Hanover, Providence, Germantown, Tulpehocken, Lancaster, Upper Milford, and Saccum congregations.

Along with a formal constitution, it adopted the name of the "German Evangelical Lutheran Ministerium of North America".

The churches of the ministerium followed a polity influenced by the Dutch Reformed model and by Muhlenberg's Pietism and did not insist on strict adherence to the Lutheran Confessions.

Mindful of this and other Lutheran church bodies founded in North America, in 1792, the group in Philadelphia renamed itself "The Ministerium of Pennsylvania and Adjacent States".

[11] In 1818, the Pennsylvania Ministerium began talks of organizing the various Lutheran church bodies in America so that they could "stand in some or another in closer connection with one another".

It was under the auspices of the General Synod, with the leadership of Samuel Simon Schmucker, that a Lutheran seminary and college were founded in Gettysburg, Pennsylvania.

[citation needed] The Pennsylvania Ministerium remained an independent Lutheran church body in the years following.

[citation needed] As with many Protestant churches, the General Synod was split on the issue of the American Civil War in the 1860s.

In 1918, following the celebration of the 400th anniversary of the Reformation, the three Lutheran church bodies of eastern America (the General Synod, the United Synod of the South, and the General Council) reunited to form the United Lutheran Church in America.