Standing at one end of Church Green, the imposing 156ft spire and impressive size of St Mary's reflects the wealth and importance of Witney in the Middle Ages; much of this wealth came from the wool trade. It is likely that the Bishops of Winchester were responsible for the founding of the current church some time between 1070 and 1100, though a Saxon church may have stood on the site before this.

By the 18th and 19th centuries many of the blanket makers were non-conformist but St Mary's still contains the graves of many of those in the trade: some of the headstones bear images of shuttles and other symbols relating to cloth making.

The church also incorporates the mortuary chapel of the Wenman family: brasses show Richard Wenman in a fur trimmed gown, a purse hanging from his belt, his two wives standing either side of him. Richard Wenman was a wealthy wool merchant, so wealthy that in 1524 he paid 80% of all the tax due in Witney!