When opened, it was the northern terminus of the Great Western Railway's Uxbridge branch from the main line at West Drayton.

In 1863, a plan was approved to construct an extension of the Uxbridge Branch to create a link northwards to Watford Junction in Hertfordshire via Rickmansworth (Church Street), connecting it to the Watford and Rickmansworth Railway (W&RR).

The Uxbridge Branch continued to be operated under British Rail until 10 September 1962, when the service from West Drayton was withdrawn and Uxbridge Vine Street station was closed to passengers.

[2][3] Goods traffic ceased two years later with the exception of the line south of the Grand Union Canal on which freight services were operated to the Middlesex Oil and Chemical Works in Yiewsley until 8 January 1979.

Demolition of Uxbridge Vine Street station occurred in 1969.