Henry Melchior Muhlenberg grew up in Eimbeck where his member of the Council. His education was interrupted after his father's death in 1723 and did not begin until he entered the University of Gottenberg in 1735. Feeling the need for instruction of poor and neglected children, he joined with several other students to establish an institution to provide instruction which still exists. He began his theological studies in 1737, went to Halle in 1738 to complete them in 1739. He continued working at the Francke orphan home until he accepted a call from three congregations in Pennsylvania and elsewhere as the need arose in 1741. He traveled to London in 1742 and left on a packet to the New World, arriving in Charleston on September 22, 1742. He spent time in both Charleston and the Ebeneezer colony of Georgia, finally arriving in Philadelphia on November 25. The peripatetic Muhlenberg worked seemingly unceasingly to expand German Lutheranism, first in New York and eventually both up and down the Atlantic seaboard. He married J. Conrad Weiser's daughter in 1745. He helped found the first Lutheran synod in what is now the United States in 1748. He spent part of the year's 1774-75 in South Carolina trying to bring peace to the Lutherans there. An American patriot, he found the War years difficult, moving to Trappe, Pennsylvania, where he remained in failing health until his death.

Muhlenberg is best known today among non-Lutherans because of his magnificent journals of his travels and life in pre-Revolutionary America. His landscape descriptions and accounts of travel are some of the most cogent for the period.