The Presbytery of Prince Edward Island consisted of three congregations on PEI and one in Massachusetts, United States, composed chiefly of emigrants from PEI. Initially, PEI formed part of the Presbytery of Ergerton, Nova Scotia, and later the Presbytery of Pictou, NS. When Church of Scotland congregations within the rest of Canada joined the Presbyterian Church of Canada, those on PEI remaining in the Presbytery of Pictou changed its name to the "Presbytery of Prince Edward Island in conjunction with the Church of Scotland."

Reverend Donald MacDonald was the first Church of Scotland minister on PEI. A native of Scotland, MacDonald's initial services were conducted in Gaelic. He began ministering in the DeSable and Murray River area circa 1826, and held the initial church services in settler's homes. MacDonald followers became known as "MacDonaldites."

A church was built in Orwell Head in 1829 and became the center of MacDonald's congregation on the east side of the Hillsborough River. New churches were built in DeSable 1855 and in Orwell Head in 1864. The church built in Murray River in 1867 was moved in 1912 from the Murray River Road to the Gladstone Road by horse and capstan.