The son of a farmer, he was born in West Lothian and educated at Edinburgh. The son of James Wilkie, a farmer, he was born at Echlin, in the parish of Dalmeny, on 5 October 1721. His father dying during his student days, he succeeded to the unexpired lease on a farm at Fishers" Tryste, near Edinburgh.
He was educated at Dalmeny parish school and Edinburgh University, having among his college contemporaries John Home, David Hume, William Robertson, and Adam Smith.
In 1757 he published the Epigoniad, dealing with the Epigoni, sons of the seven heroes who fought against Thebes. He also wrote Moral Fables in Verse. In 1756 he entered the Church, becoming minister at Ratho, Midlothian.
He was also appointed Professor of natural philosophy at the University of Street Andrews in 1759.
Licensed as a preacher by the presbytery of Linlithgow on 29 May 1745, he combined, while waiting for a charge, writing and agriculture. On 17 May 1753 he was appointed, under the patronage of the Earl of Lauderdale, assistant to John Guthrie, parish minister of Ratho, Midlothian, on whose death in 1756 he became sole incumbent.
Eccentricity—his occasionally omitting, for instance, to take off his hat before entering the pulpit—somewhat marred the success of his pastorate. In 1759 he was appointed professor of natural philosophy at Saint Andrews, where he devoted his leisure to experiments in moorland farming.
In 1766 the university conferred on Wilkie the honorary degree of Doctor of Divinity Subject to ague, he died on 10 October 1772.
Robert Fergusson, one of his students, eulogised him in a memorial eclogue.
