He was born in Knucklas, Radnorshire and may have been educated at Jesus College, Oxford (although the Oxford DNB notes there is no written record of this). He returned to Wales as a schoolmaster (1638-9) during which time he was converted to the Puritan understanding of the Gospel of Jesus Christ under the preaching of the Puritan Walter Cradock and through the writings of Richard Sibbs (1577-1635) and William Perkins (1558-1602). In about 1639 he became an itinerant preacher and for preaching in various parts of Wales he was twice arrested. In 1640, however, he was not punished and during the Civil War he preached in and around London.
On 26 December 1641 he was teaching the word of God in Llanyrne Parish Church in Ross when he was forcibly removed by Hugh Lloyd and twelve armed men and imprisoned.In 1646, when Parliament's victory was certain, Powell returned to Wales having received a "certificate of character" from the Westminster Assembly, although he had refused to be ordained by the Presbyterians. With a salary granted to him by parliament he resumed his itinerant preaching in Wales.
In 1650 Parliament appointed a commission for the better propagation and preaching of the gospel in Wales with Powell acting as one of the principal advisers of this body. For three years he was actively employed in removing from their parishes those ministers whom he regarded as incompetent. During this time he was involved in a controversy with Welsh poet Katherine Philips. Powell had published a poem celebrating the regicide of Charles I, and Philips responded with hers, Upon the Double Murder of King Charles in Answer to a Libellous Rhyme made by V.P. This was one of her first forays into political writing, and she is one of the first women to do so in literature. When it became apparent the poem may be published, and so embarrass her husband James Philips, she was forced to apologise. She did so in the form of another poem but whilst distancing herself from the views of her husband she reinforced her criticism of Powell. 
In 1653 Powell returned to London to preach at St Ann Blackfriars after the death of their pastor, William Gouge. Having denounced Cromwell for accepting the office of Lord Protector, he was imprisoned.
At the Restoration in 1660 he was arrested for preaching, and after a short period of freedom he was once again seized and incarcerated, remaining in prison for seven years. He was set free in 1667, but in the following year he was again imprisoned and was in custody until his death on 27 October 1670. Powell is buried at Bunhill Fields cemetery.
On 18 July 1660 the Council of King Charles II issued an order to Sir Matthew Price, High Sheriff of Montgomeryshire to take into safe custody Vavasour Powell (described as, "a most factious and dangerous minister"), Sir Richard Saltonstall, and Richard Price of Aberbechan.
According to Sir Matthew Price's letters to Secretary Nicholas, Vavasour Powell, Sir Richard Saltonstall and Richard Price were concerned in a plot to depose King Charles II. Letters were found in their possession indicating the plot extended all the way to London. By 2 August 1660 Vavasour Powell was taken into custody, while Sir Richard Saltonstall and Capt. Richard Price "had left these parts" [Montgomeryshire].
Powell wrote eleven books and some hymns but his chief gifts were those of a preacher. During his ministry he preached before the Lord Mayor of London (1649), Parliament (1650) and as an ardent defender of Calvinism held disputations with popular Arminians of his day.
While remaining a relatively minor figure in seventeenth-century Puritan history since his death, Powell's place in the Puritan movement has been reassessed in recent years. The twentieth-century Welsh theologian R. Tudur Jones wrote of Powell:
"Vavasor Powell deserves better of historians than to be dismissed as a millenarian enthusiast. In many ways, Powell was the most striking personality amongst the Welsh Puritans."
That estimation has been heeded as Vavasor Powell has been the subject of doctoral dissertations as well as several peer reviewed papers and presentations. Vavasor Powell has emerged as a leading case study for the right wing elements of Seventeenth Century English Non Conformity and their relationship to the larger Puritan movement.
- Stephen K. Roberts, ‘Powell, Vavasor (1617–1670)’, Oxford Dictionary of National Biography, Oxford University Press, 2004; online edn, May 2006 accessed 22 Aug 2013
- Haslam, Richard (1992). The Buildings of Wales: Powys (1 (with corrections) ed.). Penguin Books, University of Wales Press. pp. 131–136. ISBN 9780300096316. Retrieved 12 May 2015.
- Shopland, Norena 'The Welsh Sappho' from Forbidden Lives: LGBT stories from Wales,Seren Books, 2017
- Green, Mary Ann Everett, Ed. Calendar of State Papers, Domestic Series, of the Reign of Charles II, 1660-1661 Vol. I (1860) London: Longman, Green, Longman, & Roberts, p. 123
- Green, Mary Ann Everett (1860). Calendar of State Papers, Domestic Series, of the Reign of Charles II, 1660-1661 Vol. I. London: Longman, Green, Longman & Roberts. p. 176.
- M.A. Milton, The Application of the Faith of the Westminster Assembly in the Ministry of the Welsh Puritan, Vavasor Powell (1617-1670), page 15.
- William H. Brackney, A Genetic History of Baptist Thought: With Special Reference to Baptists in Britain and North America (2004); pp. 30-31.
- The Life and Death of Mr Vavasor Powell (book) (1671), attributed to Edward Bagshaw the younger;
- Vavasoris Examen et Purgamen (1654), by E Allen and others;
- Daniel Neal, History of the Puritans (1822);
- T Rees, History of Protestant Nonconformity in Wales (1861);
- R. Tudur Jones, "Vavasor Powell" (1971) and "Vavasor Powell a'r Bedyddwyr" (1949);
- "The Application of the Theology of the Westminster Assembly in the Ministry of the Welsh Puritan, Vavasor Powel (1617-1670)" (1998) by Michael A. Milton (Doctor of Philosophy  University of Wales);
- "The Pastoral Predicament of Vavasor Powell (1617-1670): Eschatological fervor and its relationship to the pastoral ministry," The Journal of the Evangelical Theological Society, September 2000.
- This article incorporates text from a publication now in the public domain: Chisholm, Hugh, ed. (1911). "Powell, Vavasor". Encyclopædia Britannica. 22 (11th ed.). Cambridge University Press. p. 223.