Prestwich-cum-Oldham traces its existence to the colony of priests whose presence gave Prestwich its name, as well as tithes, levies and terms of land-tenure related to the ancient Royal Manor of Tottington, a unit used for governance in the manorial system that spanned most of the territory.

[2] Stretching for 13 miles (21 km) from east to west from the High Middle Ages onwards, Prestwich-cum-Oldham was probably larger in extent in earlier times; documents suggest an ecclesiastical connection with Radcliffe and Middleton.

[2] By 1662, the rector of Prestwich-cum-Oldham complied with Anglicanism, but the curate of Oldham, St Mary's was expelled for preaching nonconformism; chapels at Stand and Greenacres span virtually the whole history of non-conformity in the United Kingdom, as does a Quaker meeting-house at Royton.

[2] The parish remained comparatively rural until the Industrial Revolution; some townships, such as Royton, had primitive domestic manufactories and traded goods at the markets in Rochdale and Manchester.

The introduction of the factory system to Oldham, Chadderton, Crompton and Royton led to the demise of arable land via rapid urbanisation and industrialisation.

[4] On several occasions during the 15th and 16th centuries, the Archdeacon of the Chester had to intervene because Crompton's inhabitants refused to contribute monies towards holy bread and candles used at Prestwich.