Beginning at former Highway 2 in Delaware, what is now known as Middlesex County Road 81 travels west through Campbellvale, Mount Brydges and Caradoc, curving slightly to the northwest.

[15] As a result of this work, Highway 81 was diverted to the east, removing the slight jog at McGuffin Hills Drive.

[16][5] As part of a series of budget cuts initiated by premier Mike Harris under his Common Sense Revolution platform in 1995, numerous highways deemed to no longer be of significance to the provincial network were decommissioned and responsibility for the routes transferred to a lower level of government, a process referred to as downloading.

Highway 81 was deemed to serve a local function and was transferred to Middlesex and Huron counties in two separate downloads.

[17] The remainder of the highway, between Strathroy and Grand Bend, was transferred, on January 1, decommissioning the route in the process.

[3] The following table lists the major junctions along Highway 81, as noted by the Ministry of Transportation of Ontario.