[1] The second of ten children, McDonald attended the Red River Academy until he was 15, then helped his father on the family farm for four years before taking a position with the Methodist mission at Norway House.
[2] McDonald also studied at St. John's Collegiate School (predecessor of the University of Manitoba founded in 1877), which enabled him to take holy orders as an Anglican deacon in 1852.
Using a syllabic method and Latin alphabet, McDonald began translating the Bible into Ojibwe (also known as Ojibwa or Chippewa]], and completed the minor prophets before his next assignment.
However, in 1872, he accepted an invitation of the Church Missionary Society and took a working vacation in England, shortly after the Hudson's Bay Company sold its lands to Canada, leading to the Red River Rebellion of 1869 and finally the creation of Manitoba as the country's fifth province.
In 1876, a year after McDonald received a promotion to Archdeacon of the newly created Mackenzie diocese, he married Julia Kutuq, a Gwich'in woman, with whom he eventually had nine children.
With the help of Julia and other native speakers, McDonald translated the Bible, Book of Common Prayer and many hymns into Gwich'in (which he called Takudh and, later, Tukudh).