John Heckewelder was born into a Moravian family on March 12, 1743, in Bedford, England. The Moravian Church originated in 15th-century Bohemia (now the Czech Republic) as a reform movement led by Jan Hus, devoted to having services in the vernacular language, and eliminating some of the practices that would later trigger the Protestant Reformation. For most of his first 12 years, Heckewelder attended Moravian schools. It was here that he and some of his friends were inspired by their lessons to become missionaries for the Moravian Church.

On March 12, 1754, Heckewelder's 11th birthday, he and his family left England for America. They landed in New York and then continued on to Bethlehem, Pennsylvania. Although Heckewelder was apprenticed to a cooper at the time, in 1762 his dream of becoming a missionary came true. A missionary by the name of Christopher Frederick Post had asked him along on a journey to western Pennsylvania to assist him in his missionary work with the Christian Delaware Indians there. It was here that Heckewelder began his life as a missionary and started to learn the culture and language of the Indians, something he would be considered an expert on before his tenure as missionary ended. Heckewelder was 19 at the time. Heckewelder also worked closely with another Moravian, David Zeisberger.

During his time as a missionary, Heckewelder helped found several communities in the name of the Moravian Church. In 1772, Heckewelder and Zeisberger founded Schoenbrunn for the Delaware Indians in eastern Ohio. The village prospered and they went on to found other communities such as Gnadenhutten and Lichtenau. When the Revolutionary War broke out, Heckewelder became an American agent of sorts. He would report enemy size and movements to American authorities in Pittsburgh. In 1781, Zeisberger and Heckewelder were arrested for treason by British troops and taken to Detroit for trial. While Captain Pipe opposed the Moravians politically (he was a Delaware war chief who had sided with the British), he respected what they did for his people. It was expected that Pipe would speak in favor of Heckewelder's guilt at the trial in Detroit, but instead he spoke in defense of the Moravians and thus played a major role in their release. Heckewelder was recognized for his contributions to America by General Edward Hand in the form of a written statement in 1800.

Heckewelder retired from missionary work in 1786 and returned home to Bethlehem with his wife, Sarah, and their two daughters, Polly and Anna. With another baby coming and the fear of an Indian war it was decided that the best thing to do would be to return to Bethlehem. Heckewelder's knowledge of Native American customs and language soon had him on the road again. After two years in Bethlehem, he began to aid the United States in land treaty negotiations with the Indians. He would perform this duty into the 1800's. In 1801, he moved with his family to Gnadenhutten and performed as a member of the Society for Propagating the Gospel. He returned to Bethlehem with his family in 1810. In addition to his article, "Indian History, Manners, and Customs," which appeared in The North American Review in June 1819, Heckewelder kept an extensive log of all his travels between the years 1754 to 1813. Heckewelder passed away at the age of 80 on January 31, 1823.