He was born in the parish of Troqueer, near Dumfries. After a parish school education, he was intended for a career as gardener, but entered the University of Edinburgh in 1822, Hetherington became minister of Torphichen, Linlithgow, in 1836; in the same year he married Jennie, daughter of the Rev. Dr. Meek of Hamilton.

In 1843 he adhered to the Free Church of Scotland, and in 1844 was appointed to a charge in St Andrews. He became minister of Free St. Paul's Church, Edinburgh, in 1848; and was appointed professor of apologetics and systematic theology in the Free Church College, Glasgow, in 1857.

Before completing his studies for the church he published, in 1829, Twelve Dramatic Sketches' founded on the Pastoral Poetry of Scotland, with delineations of scenery and manners.

Besides his poems Hetherington published:

• The Ministers Family, 1838, a popular evangelical work.
• History of the Church of Scotland from the Introduction of Christianity to the Period of the Disruption, May 18, 1843, 1843. A partisan book, it was preceded by an essay On the Principles and Constitution of the Church of Scotland, and reached a seventh edition in 1852.
• History of the Westminster Assembly of Divines, 1843. It was edited and annotated in 1878 by Robert Williamson.

In 1844 Hetherington established the Free Church Magazine, which he edited for four years. He also contributed to religious periodicals, especially the British and Foreign Evangelical Review, and published sermons, poems, and some shorter religious works.