Due to Milne's distinguished role in his missionary field, the University of Glasgow granted him a Doctor of Divinity (D.D.)

Milne was born in Braeside of Cults, a village few miles south to Huntly, in the rural parish of Kennethmont in Aberdeenshire, Scotland.

Soon after his conversion, Milne decided to leave the Church of Scotland, and to join "another body of Christians" which was evangelical and with edifying preaching.

Milne, with his wife and infant child were expelled by the Roman Catholic priests there after three days, and he left for Guangzhou, where he was able to begin study of the Chinese language.

His observation regarding the difficulty of an English-speaker acquiring the Chinese tongue has been frequently repeated: "Learning the Chinese language requires bodies of iron, lungs of brass, heads of oak, hands of spring steel, eyes of eagles, hearts of apostles, memories of angels, and lives of Methuselah.

Milne agreed and traveled south, distributing tracts and books, finally returning to Guangzhou on 5 September to spend the winter of 1813–1814 there.

Liang Fa later became renowned as the author of the Christian literature that inspired Hong Xiuquan and the Taiping Rebellion.

Rachel Cowie Milne gave birth to six children for William, but two of them, David (d. 4 May 1816) and Sarah (d. 10 April 1817) died in infancy.

Rachel Cowie Milne died on 20 March 1819 at Klebang, Malacca, leaving her will that her Amelia might receive proper education.

Both Robert George and William Charles Milne graduated from Homerton Academy and Marischal College of Aberdeen University.