The 76.5-kilometre (47.5 mi) route served as a southerly bypass to Highway 2, avoiding Paris, Ancaster and Hamilton.

In addition to the previously mentioned cities, Highway 53 served the communities of Cathcart and Burford.

[4] For much of its history, the road was concurrent with Highway 2 between Woodstock and Eastwood, as well as between Brantford and Ancaster.

[6] East of this point the route is known as Brant County Highway 53, where it continued southeast passing through the community of Cathcart.

The route crossed the Grand River west of downtown, intersecting and becoming concurrent with former Highway 2 at Brant Avenue.

[5] At its western terminus, the route intersected Highway 2 in Eastwood, then travelled concurrently with it for 7.7 km (4.8 mi) west into Woodstock.

To connect the two sections of the route, a concurrency was established along Highway 2 between Brantford and Duff's Corners.

[14][15] The following table lists the major junctions along Highway 53, as noted by the Ministry of Transportation of Ontario.