Cathcart was the place where an important route from Glasgow to Ayrshire crossed the Cart by ford and later by stone bridge. The road led through Gorbals to the farm of Mains of Cathcart, then through the village passing the churchyard and the smiddy, for long the establishment of the Peddies, hereditary armourers to the Earl of Cathcart. The route passed the mill before crossing the river and turning south towards Kilmarnock in Ayrshire. The bridge has a date of 1624, possibly a re-insertion into an 18th century reconstruction.
After the Reformation the church was under the charge of Protestant readers (lay preachers) until Robert Hamilton was raised to the status of minister in 1628. Later ministers were embroiled in the religious and political controversies of the late 17th century. A church seems to have been erected in 1707 beside St Oswald's holy well and rebuilt in 1744. The earliest known parish schoolmaster in Cathcart was Thomas Pettigrew who accepted the office in 1701. His schoolhouse stood at the top of Manse Brae until the 1930s.
The pure and abundant water of the Cart made paper-making an early and important industry. The first of four paper mills in the parish was established at Newlands in 1682 by a Frenchman, Nicholas Deschamp, an experienced paper-maker who had previously worked in Edinburgh. His son-in-law, James Hall, son of the meal miller, began a second paper mill upriver from Cathcart at Netherlee. Both mills were replaced in 1730 by a new paper mill at Millholm which survived for almost two centuries.