The parish of Cowley was mentioned in the 1086 Domesday Book, its independent male householders were two villagers, one cottage-owner with one cultivated ploughland.

A lay franchise (jurisdiction) of the church was held in 1293 by Lucy Peachey, whose name is reflected in several of the roads and by the local government ward of Cowley Peachey.

Cowley was surrounded by Hillingdon parish, of which the town of Uxbridge itself and Uxbridge Moor, which separated Cowley from Buckinghamshire on the west, formed part. Within the triangle formed where the River Pinn and Fray's River meet, Cowley parish was so intermixed with Hillingdon that parts of it were entirely detached from the rest, while other parts, some detached, lay farther east across the Pinn.

In the west, along the main road between Uxbridge and West Drayton, and mostly to the north of the Iver Lane turning, lay the village formerly known as Cowley Street, mostly in Cowley parish. This hamlet and the church hamlet formed the main areas of settlement within the parish, though there were a few houses elsewhere, including some at what is now called Cowley Peachey, the southern part of Cowley.

During the 19th century increasing amounts of land were given over to market- and nursery-gardens, and to brickworks. About 1800 the stretch of the Grand Junction Canal through Cowley was opened, and packet boats ran for a while in 1801 and occasionally in the next few years between Uxbridge and London.

From 1836 to 10 September 1962 there was a railway line between West Drayton and Uxbridge, with an intermediate station at Cowley (opened 1 October 1904). There is still a Station Road, which bridges where the tracks once were.

Cowley remained an almost entirely rural village until after World War I

Cowley became part of the urban district of Uxbridge in 1929 and part of Uxbridge civil parish in 1937.