Salesbury was born in about 1520 in the parish of Llansannan, Conwy. He was educated at Oxford University, where he studied the Hebrew, Greek and Latin languages, and also became familiar with the (banned) writings of Martin Luther and William Tyndale as well as the technology of printing.
In 1547, Salesbury produced an English-Welsh dictionary called A dictionary in Englyshe and Welshe, and in 1550 his A briefe and a playne introduction, teachyng how to pronounce the letters in the British tong (now commenly called Walsh)... was printed by Robert Crowley. A revised edition was printed "by Henry Denham for Humfrey Toy, dwellyng at the sygne of the Helmet in Paules church yarde, The. xvij. of May. 1567." Both of these books have become important sources for information about the spoken English of the sixteenth century.
In 1550, he published Ban wedy i dynny air yngair allan o hen gyfreith Howel da vap Cadell brenhin Kymbry ynghylch chwechant mlynedd aeth heibio wrth yr hwn van y gellir deall bot yr offeiriait y pryd hynny yn priodi gwragedd yn ddichwith ac yn kyttal ac wynt in gyfreithlawn. A certaine case extracte[d] out of the auncient law of Hoel da, kyng of Wales in the yere of oure Lorde, nyne hundred and fourtene passed: whereby it maye gathered that priestes had lawfully married wyues at that tyme. This book, printed by Robert Crowley, was in Welsh and English; as the title indicates, it was an attempt to justify Protestant doctrine in favour of a clerical marriage to the Welsh and English by establishing precedent for it in the "auncient law" of a Welsh king. (It was no doubt significant that the present royal family, the Tudors, had Welsh origins.) Also in 1550, a polemical text appeared under Crowley's imprint stating that it was "compiled" by Salesbury: The baterie of the Popes Botereulx, commonly called the high altare. A third Salesbury book with Crowley's imprint in 1551 is a translation of the epistle and gospel readings from the 1549 Book of Common Prayer: Kynniuer llith a ban or yscrythur lan ac a d’arlleir yr eccleis pryd commun, y sulieu a’r gwilieu trwy’r vlwyd’yn: o Cambereiciat.
The belief of Erasmus and Luther that the Bible should be available to all in their native language was firmly advocated by Salesbury. With the succession of Elizabeth I, Salesbury went to work on this project. In 1563, he helped instigate an act of parliament under which the translation of the Bible became a priority for the bishops of Wales and Hereford. Quite possibly a confederate in this project, Robert Crowley, Salesbury's former printer, was at this time a Canon of Hereford, having been instituted to the stall or prebend of "Pratum majus" in the cathedral of Hereford c. 1560-63.
Salesbury worked with Richard Davies (Bishop of St. David's) and Thomas Huet (Precentor of St David's) to prepare a translation of the New Testament from the original Greek into Welsh. This was published on 7 October 1567. He also translated the English Book of Common Prayer into Welsh, which was also published in 1567 as Y Llyfr Gweddi Gyffredin), both were published by Humphrey Toy.
- Salesbury, William (1998). Meic Stephens (Ed.), ed. The new companion to the literature of Wales. Cardiff: University of Wales Press. ISBN 0-7083-1383-3.
- Parry, Thomas (1955). A history of Welsh literature. Translated by H. Idris Bell. Oxford: Clarendon Press.
- Andrew Breeze, "William Salesbury," The Dictionary of Literary Biography, Volume 281: British Rhetoricians and Logicians, 1500–1660, Second Series, Detroit: Gale, 2003, pp. 260–273.
- R. Brinley Jones, "Geirfa Rhethreg 1552-1632," Ysgrifau Beirniadol, vol. 9, 1976, 118-146.
- Isaac Thomas, "William Salesbury and his Testament", Cardiff : University of Wales Press, 1967 / Isaac Thomas, "William Salesbury a'i Destament", Caerdydd : Gwasg Prifysgol Cymru, 1967.
- W. Alun Mathias, "Llyfr Rhetoreg William Salesbury," Llen Cymru, vol. 1, 1951, pp. 259–268, and vol. 2, 1952, pp. 71–81.