Henry was born at Broad Oak, Iscoyd, a farmhouse on the borders of Flintshire and Shropshire, Wales, United Kingdom. His father, Philip Henry, was a Church of England cleric and had just been ejected under the Act of Uniformity 1662. Unlike most of his fellow-sufferers, Philip possessed some private means, and was thus able to give his son a good education. Matthew went first to a school at Islington, at that time a village just outside London, and then to Gray's Inn, in the heart of the capital. He soon gave up his legal studies for theology, and in 1687 became minister of a Presbyterian congregation at Chester. While in Chester, Henry founded the Presbyterian Chapel in Trinity Street. He moved again in 1712 to Mare Street, Hackney. Two years later (22 June 1714), he died suddenly of apoplexy at the Queen's Aid House (41 High Street) in Nantwich, while on a journey from Chester to London.
Matthew Henry's well-known six-volume Exposition of the Old and New Testaments (1708–10) or Complete Commentary, provides an exhaustive verse by verse study of the Bible. covering the whole of the Old Testament, and the Gospels and Acts in the New Testament. After the author's death, the work was finished (Romans through Revelation) by thirteen other nonconformist ministers, partly based upon notes taken by Henry's hearers, and edited by George Burder and John Hughes in 1811.
Henry's commentaries are primarily exegetical, dealing with the scripture text as presented, with his prime intention being explanation, for practical and devotional purposes. While not being a work of textual research, for which Henry recommended Matthew Poole's Synopsis Criticorum, Henry's Exposition gives the result of a critical account of the original as of his time, with practical application. It was considered sensible and stylish, a commentary for devotional purposes.
Famous evangelical Protestant preachers such as George Whitefield and Charles Spurgeon used and heartily commended the work, with Whitefield reading it through four times – the last time on his knees. Spurgeon stated, "Every minister ought to read it entirely and carefully through once at least."  John Wesley wrote of Henry:
He is allowed by all competent judges, to have been a person of strong understanding, of various learning, of solid piety, and much experience in the ways of God. And his exposition is generally clear and intelligible, the thoughts being expressed in plain words: It is also found, agreeable to the tenor of scripture, and to the analogy of faith. It is frequently full, giving a sufficient explication of the passages which require explaining. It is in many parts deep, penetrating farther into the inspired writings than most other comments do. It does not entertain us with vain speculations, but is practical throughout: and usually spiritual too teaching us how to worship God, not in form only, but in spirit and in truth.
Henry's Miscellaneous Writings, including a Life of Mr. Philip Henry, The Communicant's Companion, Directions for Daily Communion with God, A Method for Prayer, A Scriptural Catechism, and numerous sermons, the life of his father, tracts, and biography of eminent Christians, together with the sermon on the author's death by William Tong were edited in 1809; and in 1830 a new edition included sermons not previously included and Philip Henry's "What Christ is made to believers". The collection was issued several times by different publishers.
Several abbreviated editions of the Commentary were published in the twentieth century; more recently the Christian linguist and author of reference books, Martin H. Manser, edited a version in modern English: The New Matthew Henry Commentary: The Classic Work with Updated Language (Zondervan 2010).
- Henry, Matthew (1833). The Miscellaneous Works of the Rev. Matthew Henry: Containing in Addition to Those Heretofore Published 1. London: Joseph Ogle Robinson.
- —— (1833). The Miscellaneous Works of the Rev. Matthew Henry: Containing in Addition to Those Heretofore Published 2. London: Joseph Ogle Robinson.
Following other reformed Christian theologians, the subject identifies the 'man of sin', the focus of latter day apostasy, and the Antichrist as the papacy in his interpretation of 2 Thessalonians ii, 3. The theologian lists three 'blasphemous titles' that he states have been attached to the 'bishops of Rome'.
Perhaps his best-known quotation is about the relationship between men and women, from the story of the creation of Eve, in the Book of Genesis:
The woman was made of a rib out of the side of Adam; not made out of his head to rule over him, nor out of his feet to be trampled upon by him, but out of his side to be equal with him, under his arm to be protected, and near his heart to be beloved.
In 1860 a memorial was erected in Chester to commemorate Matthew Henry. This consists of an obelisk designed by Thomas Harrison that incorporates a bronze medallion by Matthew Noble. The obelisk originally stood in the churchyard of St Bridget's Church, and was moved in the 1960s to stand on a roundabout opposite the entrance to Chester Castle.
- Religious Tract Society, Christian Biography: Lives of William Cowper, Mrs. Ann H. Judson, Anna Jane Linnard, Matthew Henry, 1799, Matthew Henry
- Morris, Edward; Roberts, Emma (2012), Public Sculpture of Cheshire and Merseyside (excluding Liverpool), Public Sculpture of Britain 15, Liverpool: Liverpool University Press, pp. 66–67, ISBN 978-1-84631-492-6
- Images of England: 41 High Street, Nantwich
- "Matthew Henry Commentary on the Whole Bible" (6 volumes). Bible. Christianity. Retrieved 2007-10-11.
- "Matthew Henry Nonconformist minister and Bible commentator". Christian Biography Resources. Wholesome words. Retrieved 2011-09-19.
- "General Information", Henry, Matthew, Blue Letter Bible, 19 Sep 2010 [1 Mar 1996], archived from the original on 9 October 2012
- Schaff, Philip, "Matthew Henry", The New Schaff-Herzog Encyclopedia of Religious Knowledge V, TLogical
- Commenting and Commentaries, p. 3
- Wesley, John, Preface to the Old Testament Notes, NNU, retrieved 23 September 2015
- "Matthew Henry's Miscellaneous Writings". Copac. Retrieved 5 December 2009.
- Henry, Matthew. (1991). Matthew Henry's commentary. v.6 (New Modern ed.) Peabody, Mass. : Hendrickson Publishers. p. 643. ISBN 9781598564358
- "Genesis 2". Bible Study Tools. Retrieved 15 March 2016.
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