An earnest and well-loved clergyman. Guthrie was born at Pitforthy (Angus), the eldest of five brothers, four of whom entered the ministry. He was educated at St Andrews University under his cousin, Professor James Guthrie (d.1661). Guthrie was ordained in 1644 and ministered in the village of Fenwick (East Ayrshire), a new parish, greatly in need of his services. He resisted the imposition of Bishops in the Church of Scotland, promoted by King Charles II, and was forced from his charge in 1661.
Guthrie died at Brechin and is also remembered for his book A Christian's Great Interest.